mTOR in Down syndrome: Role in Aß and tau neuropathology and transition to Alzheimer disease-like dementia

Di Domenico, Fabio; Tramutola, Antonella; Foppoli, Cesira; Head, Elizabeth; Perluigi, Marzia; Butterfield, D. Allan

doi:10.1016/j.freeradbiomed.2017.08.009

Cited by 89Alzheimer's disease research and treatmentsDown syndrome and intellectual disability researchDementia and Cognitive Impairment Research

mTOR in Down syndrome: Role in Aß and tau neuropathology and transition to Alzheimer disease-like dementia

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Di Domenico, Fabio, Tramutola, Antonella, Foppoli, Cesira, Head, Elizabeth, Perluigi, Marzia, Butterfield, D. Allan·2018·Free Radical Biology and Medicine

DOI 10.1016/j.freeradbiomed.2017.08.009PMC PMC5748251

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Abstract

The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase involved in the regulation of protein synthesis and degradation, longevity and cytoskeletal formation. The mTOR pathway represents a key growth and survival pathway involved in several diseases such as cancer, obesity, cardiovascular disease and neurodegenerative diseases. Numerous studies linked the alterations of mTOR pathway to age-dependent cognitive decline, pathogenesis of Alzheimer disease (AD) and AD-like dementia in Down syndrome (DS). DS is the most frequent chromosomal abnormality that causes intellectual disability. The neuropathology of AD in DS is complex and involves impaired mitochondrial function, defects in neurogenesis, increased oxidative stress, altered proteostasis and autophagy networks as a result of triplication of chromosome 21(chr 21). The chr21 gene products are considered a principal neuropathogenic moiety in DS. Several genes involved respectively in the formation of senile plaques and neurofibrillary tangles (NFT), two main pathological hallmarks of AD, are mapped on chr21. Further, in subjects with DS the activation of mTOR signaling contributes to Aβ generation and the formation of NFT. This review discusses recent research highlighting the complex role of mTOR associated with the presence of two hallmarks of AD pathology, senile plaques (composed mostly of fibrillar Aß peptides), and NFT (composed mostly of hyperphosphorylated tau protein). Oxidative stress, associated with chr21-related Aβ and mitochondrial alterations, may significantly contribute to this linkage of mTOR to AD-like neuropathology in DS.

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mTOR-mediated events may help explain why type 2 diabetes is a significant risk factor for Alzheimer disease.
“These mTOR-mediated events may help explain the observation that type 2 diabetes (T2DM) is a significant risk factor for development of AD7,41.”
From Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease (2019) · cites this paper as [41]
The Introduction and section 2 link mTOR to insulin signaling and to amyloid pathology in Alzheimer disease, supporting a possible mechanistic connection. Our copy does not state that type 2 diabetes is a significant risk factor for developing Alzheimer disease; that point appears only in the title of another work listed in the References. No page numbers are available in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measured
Activated mTORC1 regulates protein synthesis, autophagy, mitochondrial function, lipogenesis, ketogenesis, and insulin signaling, is linked to glucose metabolism, and is activated by growth factors, amino acids, and high cellular energy status.
“Activated mTORC1 is intimately involved in regulation of protein synthesis, autophagy, mitochondrial function, lipogenesis, ketogenesis, and insulin signaling, and is crucially linked to glucose metabolism, where it becomes activated by growth factors, amino acids, and high cellular energy status41,42 (Fig 2).”
From Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease (2019) · cites this paper as [41]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
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Oxidative or nitrosative damage to multiple proteins, including synaptic proteins, very likely contributes to memory problems and other cognitive deficits, reduced neuronal ATP availability, and decreased clearance of abnormal proteins in Alzheimer disease.
“In summary, oxidative and/or nitrosative damage to multiple proteins, including synaptic proteins is very likely to contribute to the memory problems and other cognitive deficits, reduced ATP availability in neurons, and decreased clearance of abnormal proteins34, creating a “perfect storm” (or sTORm perhaps!) of detrimental cognitive effects in AD9,34,35,41,42.”
From Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease (2019) · cites this paper as [41]
Section 2.1 reports oxidative damage to several protein-clearance components in Down syndrome brain, associated with reduced proteasome activity and autophagosome formation; section 3.1 links oxidative modification of lysosomal proteins to potentially reduced autophagy. The paper does not establish that damage to synaptic proteins causes memory or other cognitive deficits, or that protein oxidation reduces neuronal ATP availability in Alzheimer disease. Its reduced-ATP discussion in section 2.2 concerns neuronal progenitor cells from a Down syndrome mouse model, not that proposed causal link. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Insulin resistance is a harmful consequence of mTOR activation in amnestic mild cognitive impairment and Alzheimer disease brain.
“Insulin resistance is another detrimental consequence of mTOR activation in aMCI and AD brain41 (Fig 2).”
From Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease (2019) · cites this paper as [41]
The Introduction describes a mechanism by which mTOR activation can impair insulin signaling in the brain: it activates p70S6K, leading to IRS-1 degradation. Section 3.1, however, frames the resulting metabolic harm as a hypothesis about Down syndrome brain. The paper does not establish insulin resistance as a consequence of mTOR activation specifically in aMCI and AD brain. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Impaired autophagy is present in early Alzheimer disease and is also found in amnestic mild cognitive impairment and preclinical Alzheimer disease brains.
“This significant mediator of neuronal death is present in the early stages of AD, and evidence of impaired autophagy is also found in aMCI brain and PCAD brains41–43.”
From Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease (2019) · cites this paper as [41]
Section 2.1 (page unavailable) says autophagy is impaired in AD brains, supporting that part of the claim. It reports reduced autophagosome formation early in Down syndrome brains, not specifically in early AD, aMCI, or preclinical AD brains. The reference list names a study of mTOR signaling across preclinical AD, aMCI, and late-stage AD, but this paper does not state that impaired autophagy was found in those groups. (LLM, conf=0.85)
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Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351 · see citing works
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359 · see citing works
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
Kim, J., Kundu, M., Viollet, B., & Guan, K.-L. (2011) · Nature Cell Biology · doi:10.1038/ncb2152 · Cited by 7,227 · see citing works
Autophagy: Renovation of Cells and Tissues
Mizushima, N., & Komatsu, M. (2011) · Cell · doi:10.1016/j.cell.2011.10.026 · Cited by 6,467 · see citing works
TOR signaling in growth and metabolism
Wullschleger, S., Loewith, R., & Hall, M. N. (2006) · Cell · doi:10.1016/j.cell.2006.01.016 · Cited by 5,787 · see citing works
Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo
Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., Rowan, M. J., & Selkoe, D. J. (2002) · Nature · doi:10.1038/416535a · Cited by 4,291 · see citing works
The microRNA Registry
Griffiths-Jones, S. (2004) · Nucleic Acids Res. · doi:10.1093/nar/gkh023 · Cited by 2,446 · see citing works
Natural oligomers of the amyloid-β protein specifically disrupt cognitive function
Cleary, J. P., Walsh, D. M., Hofmeister, J. J., Shankar, G. M., Kuskowski, M. A., Selkoe, D. J., & Ashe, K. H. (2004) · Nature Neuroscience · doi:10.1038/nn1372 · Cited by 1,677 · see citing works
mTOR signaling: At the crossroads of plasticity, memory and disease
Hoeffer, C. A., & Klann, E. (2010) · Trends in Neurosciences · doi:10.1016/j.tins.2009.11.003 · Cited by 1,128 · see citing works
Autophagy Induction and Autophagosome Clearance in Neurons: Relationship to Autophagic Pathology in Alzheimer's Disease
Boland, B., Kumar, A., Lee, S., Platt, F. M., Wegiel, J., Yu, W. H., & Nixon, R. A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0800-08.2008 · Cited by 1,119 · see citing works
Active-Site Inhibitors of mTOR Target Rapamycin-Resistant Outputs of mTORC1 and mTORC2
Feldman, M. E., Apsel, B., Uotila, A., Loewith, R., Knight, Z. A., Ruggero, D., & Shokat, K. M. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000038 · Cited by 1,080 · see citing works
Inhibition of mTOR by Rapamycin Abolishes Cognitive Deficits and Reduces Amyloid-β Levels in a Mouse Model of Alzheimer's Disease
Spilman, P., Podlutskaya, N., Hart, M. J., Debnath, J., Gorostiza, O., Bredesen, D., Richardson, A., Strong, R., & Galvan, V. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009979 · Cited by 1,033 · see citing works
Evidence that production and release of amyloid beta-protein involves the endocytic pathway
Koo, E. H., & Squazzo, S. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32449-3 · Cited by 989 · see citing works
Structure of mammalian AMPK and its regulation by ADP
Xiao, B., Sanders, M. J., Underwood, E., Heath, R., Mayer, F. V., Carmena, D., Jing, C., Walker, P. A., Eccleston, J. F., Haire, L. F., et al. (2011) · Nature · doi:10.1038/nature09932 · Cited by 926 · see citing works
Molecular Interplay between Mammalian Target of Rapamycin (mTOR), Amyloid-β, and Tau
Caccamo, A., Majumder, S., Richardson, A., Strong, R., & Oddo, S. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.100420 · Cited by 881 · see citing works
The secretases: enzymes with therapeutic potential in Alzheimer disease
De Strooper, B., Vassar, R., & Golde, T. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2009.218 · Cited by 799 · see citing works
O-GlcNAcylation regulates phosphorylation of tau: A mechanism involved in Alzheimer's disease
Liu, F., Iqbal, K., Grundke-Iqbal, I., Hart, G. W., & Gong, C.-X. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400348101 · Cited by 775 · see citing works
Autophagy, amyloidogenesis and Alzheimer disease
Nixon, R. A. (2007) · Journal of Cell Science · doi:10.1242/jcs.019265 · Cited by 749 · see citing works
NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21
Arron, J. R., Winslow, M. M., Polleri, A., Chang, C.-P., Wu, H., Gao, X., Neilson, J. R., Chen, L., Heit, J. J., Kim, S. K., et al. (2006) · Nature · doi:10.1038/nature04678 · Cited by 698 · see citing works
Autophagy Failure in Alzheimer's Disease – Locating the Primary Defect
Nixon, R., & Yang, D.-S. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.01.021 · Cited by 634 · see citing works
Mechanisms of tau-induced neurodegeneration
Iqbal, K., Liu, F., Gong, C.-X., Alonso, A. D. C., & Grundke-Iqbal, I. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0486-3 · Cited by 628 · see citing works
Tau fragmentation, aggregation and clearance: the dual role of lysosomal processing
Wang, Y., Martinez-Vicente, M., Krüger, U., Kaushik, S., Wong, E., Mandelkow, E.-M., Cuervo, A. M., & Mandelkow, E. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp367 · Cited by 617 · see citing works
A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome
Wiseman, F. K., Al-Janabi, T., Hardy, J., Karmiloff-Smith, A., Nizetic, D., Tybulewicz, V. L. J., Fisher, E. M. C., & Strydom, A. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3983 · Cited by 562 · see citing works
Increased App expression in a mouse model of Down’s syndrome disrupts NGF transport and causes cholinergic neuron degeneration
Salehi, A., Delcroix, J.-D., Belichenko, P. V., Zhan, K., Wu, C., Valletta, J. S., Takimoto-Kimura, R., Kleschevnikov, A. M., Sambamurti, K., Chung, P. P., et al. (2006) · Neuron · doi:10.1016/j.neuron.2006.05.022 · Cited by 543 · see citing works
-Amyloid Oligomers Induce Phosphorylation of Tau and Inactivation of Insulin Receptor Substrate via c-Jun N-Terminal Kinase Signaling: Suppression by Omega-3 Fatty Acids and Curcumin
Ma, Q.-L., Yang, F., Rosario, E. R., Ubeda, O. J., Beech, W., Gant, D. J., Chen, P. P., Hudspeth, B., Chen, C., Zhao, Y., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.1071-09.2009 · Cited by 536 · see citing works
Autophagy and aging: keeping that old broom working
Cuervo, A. M. (2008) · Trends in Genetics · doi:10.1016/j.tig.2008.10.002 · Cited by 527 · see citing works
Sirtuin 1 Reduction Parallels the Accumulation of Tau in Alzheimer Disease
Julien, C., Tremblay, C., Émond, V., Lebbadi, M., Salem, N., Bennett, D. A., & Calon, F. (2008) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181922348 · Cited by 467 · see citing works
Alzheimer Disease and Oxidative Stress
Perry, G., Cash, A. D., & Smith, M. A. (2002) · BioMed Research International · doi:10.1155/s1110724302203010 · Cited by 455 · see citing works
Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome
Holtzman, D. M., Santucci, D., Kilbridge, J., Chua-Couzens, J., Fontana, D. J., Daniels, S. E., Johnson, R. M., Chen, K., Sun, Y., Carlson, E., et al. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.23.13333 · Cited by 448 · see citing works
A rapamycin-sensitive pathway down-regulates insulin signaling via phosphorylation and proteasomal degradation of insulin receptor substrate-1.
Haruta, T., Uno, T., Kawahara, J., Takano, A., Egawa, K., Sharma, P. M., Olefsky, J., & Kobayashi, M. (2000) · Molecular Endocrinology · doi:10.1210/mend.14.6.0446 · Cited by 437 · see citing works
Elevated risk of type 2 diabetes for development of Alzheimer disease: A key role for oxidative stress in brain
Butterfield, D. A., Di Domenico, F., & Barone, E. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.06.010 · Cited by 402 · see citing works
Self-citation
A second cytotoxic proteolytic peptide derived from amyloid β-protein precursor
Lu, D. C.-T., Rabizadeh, S., Chandra, S. S., Shayya, R. F., Ellerby, L., Ye, X., Salvesen, G. S., Koo, E. H., & Bredesen, D. E. (2000) · Nature Medicine · doi:10.1038/74656 · Cited by 395 · see citing works
Tau degradation: The ubiquitin–proteasome system versus the autophagy-lysosome system
Lee, M. J., Lee, J. H., & Rubinsztein, D. C. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.03.001 · Cited by 364 · see citing works
Alteration of mTOR signaling occurs early in the progression of Alzheimer disease (AD): analysis of brain from subjects with pre‐clinical AD, amnestic mild cognitive impairment and late‐stage AD
Tramutola, A., Triplett, J. C., Di Domenico, F., Niedowicz, D. M., Murphy, M. P., Coccia, R., Perluigi, M., & Butterfield, D. A. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13037 · Cited by 347 · see citing works
Self-citation
The kinase DYRK phosphorylates protein-synthesis initiation factor eIF2Bɛ at Ser539 and the microtubule-associated protein tau at Thr212: potential role for DYRK as a glycogen synthase kinase 3-priming kinase
Woods, Y. L., Cohen, P., Becker, W. B., Jakes, R., Goedert, M., Wang, X., & Proud, C. G. (2001) · Biochemical Journal · doi:10.1042/bj3550609 · Cited by 343 · see citing works
mTOR signaling in aging and neurodegeneration: at the crossroad between metabolism dysfunction and impairment of autophagy
Perluigi, M., Di Domenico, F., & Butterfield, D. A. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.03.014 · Cited by 339 · see citing works
Self-citation
PI3-kinase/Akt/mTOR signaling: Impaired on/off switches in aging, cognitive decline and Alzheimer's disease
Neill, C. O. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2013.02.025 · Cited by 292 · see citing works
Alzheimer’s-related endosome dysfunction in Down syndrome is Aβ-independent but requires APP and is reversed by BACE-1 inhibition
Jiang, Y., Mullaney, K. A., Peterhoff, C. M., Che, S., Schmidt, S. D., Boyer‐Boiteau, A., Ginsberg, S. D., Cataldo, A. M., Mathews, P. M., & Nixon, R. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908953107 · Cited by 288 · see citing works
DYRK1A-mediated Hyperphosphorylation of Tau
Ryoo, S., Jeong, H. K., Radnaabazar, C., Yoo, J.-J., Cho, H.-J., Lee, H. W., Kim, I.-S., Cheon, Y. H., Ahn, Y. S., Chung, S., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m707358200 · Cited by 285 · see citing works
Autophagic-lysosomal perturbation enhances tau aggregation in transfectants with induced wild-type tau expression
Hamano, T., Gendron, T. F., Causevic, E., Yen, S., Lin, W., Isidoro, C., DeTure, M., & Ko, L. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06084.x · Cited by 283 · see citing works
PI3K-AKT-mTOR signaling in prostate cancer progression and androgen deprivation therapy resistance
Hsieh, A., & Edlind, M. P. (2014) · Asian Journal of Andrology · doi:10.4103/1008-682x.122876 · Cited by 275 · see citing works
Overexpression of Dyrk1A contributes to neurofibrillary degeneration in down syndrome
Liu, F., Liang, Z., Wegiel, J., Hwang, Y., Iqbal, K., Grundke‐Iqbal, I., Ramakrishna, N., & Gong, C. (2008) · The FASEB Journal · doi:10.1096/fj.07-104539 · Cited by 272 · see citing works
Regulation of the aging process by autophagy.
Salminen, A., & Kaarniranta, K. (2009) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2009.03.004 · Cited by 270 · see citing works
The Emerging Link between O-GlcNAc and Alzheimer Disease
Zhu, Y., Shan, X., Yuzwa, S. A., & Vocadlo, D. J. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.r114.601351 · Cited by 267 · see citing works
mTOR: A pathogenic signaling pathway in developmental brain malformations
Crino, P. B. (2011) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2011.07.008 · Cited by 266 · see citing works
Dysregulation of the mTOR pathway mediates impairment of synaptic plasticity in a mouse model of Alzheimer's disease
Ma, T., Hoeffer, C. A., Capetillo-Zarate, E., Yu, F., Wong, H., Lin, M. T., Tampellini, D., Klann, E., Blitzer, R. D., & Gouras, G. K. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012845 · Cited by 262 · see citing works
Intraneuronal Aβ42 accumulation in Down syndrome brain: Original Articles
Mori, C., Spooner, E. T., Wisniewski, K. E., Wisniewski, T. M., Yamaguchi, H., Saido, T. C., Tolan, D. R., Selkoe, D. J., & Lemere, C. A. (2002) · Amyloid · doi:10.3109/13506120208995241 · Cited by 255 · see citing works
Intraneuronal Aβ-Amyloid Precedes Development of Amyloid Plaques in Down Syndrome
Gyure, K. A., Durham, R., Stewart, W. F., Smialek, J. E., & Troncoso, J. C. (2001) · Archives of Pathology & Laboratory Medicine · doi:10.5858/2001-125-0489-iaapdo · Cited by 248 · see citing works
O-GlcNAc and neurodegeneration: biochemical mechanisms and potential roles in Alzheimer's disease and beyond
Yuzwa, S. A., & Vocadlo, D. J. (2014) · Chemical Society Reviews · doi:10.1039/c4cs00038b · Cited by 247 · see citing works
Gene expression profiling in the adult Down syndrome brain
Lockstone, H. E., Harris, L. W., Swatton, J. E., Wayland, M. T., Holland, A. J., & Bahn, S. (2007) · Genomics · doi:10.1016/j.ygeno.2007.08.005 · Cited by 240 · see citing works
Hyperphosphorylation of tau in PHF.
Morishima-kawashima, M., Hasegawa, M., Takio, K., Suzuki, M., Yoshida, H., Watanabe, A., Titani, K., & Ihara, Y. (1995) · Neurobiology of Aging · doi:10.1016/0197-4580(95)00027-c · Cited by 238 · see citing works
DYRK1A and DYRK3 Promote Cell Survival through Phosphorylation and Activation of SIRT1
Guo, X., Williams, J. G., Schug, T. T., & Li, X. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.102574 · Cited by 237 · see citing works
mTOR SignalingPreprint
Laplante, M., & Sabatini, D. M. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a011593 · Cited by 235 · see citing works
Chronic Overexpression of the Calcineurin Inhibitory Gene DSCR1 (Adapt78)Is Associated with Alzheimer's Disease
Ermak, G., Morgan, T. E., & Davies, K. J. A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102829200 · Cited by 216 · see citing works
mTOR/p70S6k signalling alteration by Aβ exposure as well as in APP‐PS1 transgenic models and in patients with Alzheimer's disease
Lafay‐Chebassier, C., Paccalin, M., Page, G., Barc‐Pain, S., Perault‐Pochat, M. C., Gil, R., Pradier, L., & Hugon, J. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03187.x · Cited by 211 · see citing works
Neuronal overexpression of APPL, the Drosophila homologue of the amyloid precursor protein (APP), disrupts axonal transport
Torroja, L., Chu, H., Kotovsky, I., & White, K. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80215-2 · Cited by 203 · see citing works
Dual roles for autophagy: Degradation and secretion of Alzheimer's disease Aβ peptide
Nilsson, P., & Saido, T. C. (2014) · BioEssays · doi:10.1002/bies.201400002 · Cited by 202 · see citing works
Autophagic/lysosomal dysfunction in Alzheimer’s disease
Orr, M. E., & Oddo, S. (2013) · Alzheimer's Research & Therapy · doi:10.1186/alzrt217 · Cited by 199 · see citing works
Roles of AMP-activated Protein Kinase in Alzheimer’s Disease
Cai, Z., Yan, L., Li, K., Quazi, S. H., & Zhao, B. (2012) · NeuroMolecular Medicine · doi:10.1007/s12017-012-8173-2 · Cited by 191 · see citing works
Trisomy-driven overexpression of DYRK1A kinase in the brain of subjects with down syndrome
Dowjat, W. K., Adayev, T., Kuchna, I., Nowicki, K., Palminiello, S., Hwang, Y. W., & Wegiel, J. (2007) · Neuroscience Letters · doi:10.1016/j.neulet.2006.11.026 · Cited by 190 · see citing works
mTOR‐dependent signalling in Alzheimer's disease
Pei, J., & Hugon, J. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00509.x · Cited by 190 · see citing works
The PI3K-Akt-mTOR pathway regulates Aβ oligomer induced neuronal cell cycle events
Bhaskar, K., Miller, M., Chludzinski, A., Herrup, K., Zagorski, M., & Lamb, B. T. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-14 · Cited by 177 · see citing works
Renaming the DSCR1 / Adapt78 gene family as RCAN : regulators of calcineurin
Davies, K. J. A., Ermak, G., Rothermel, B. A., Pritchard, M. A., Heitman, J., Ahnn, J., Henrique‐Silva, F., Crawford, D. R., Canaider, S., Strippoli, P., et al. (2007) · The FASEB Journal · doi:10.1096/fj.06-7246com · Cited by 168 · see citing works
Positive and negative regulation of APP amyloidogenesis by sumoylation
Li, Y., Wang, H., Wang, S., Quon, D. H., Liu, Y.-W., & Cordell, B. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0235361100 · Cited by 165 · see citing works
Activation of mTOR: a culprit of Alzheimer&rsquo;s disease?
Cai, Z., Zhou, Y., Xiao, M., Yan, L.-J., & He, W. (2015) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s75717 · Cited by 161 · see citing works
Convergence of Amyloid-β and Tau Pathologies on Mitochondria In Vivo
Eckert, A., Schulz, K. L., Rhein, V. F., & Götz, J. (2010) · Molecular Neurobiology · doi:10.1007/s12035-010-8109-5 · Cited by 158 · see citing works
Autophagy, a guardian against neurodegeneration
Garcı́a-Arencibia, M., Hochfeld, W. E., Toh, P. P. C., & Rubinsztein, D. C. (2010) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2010.02.008 · Cited by 157 · see citing works
Neuropathological role of PI3K/Akt/mTOR axis in Down syndrome brain
Perluigi, M., Pupo, G., Tramutola, A., Cini, C., Coccia, R., Barone, E., Head, E., Butterfield, D. A., & Di Domenico, F. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.04.007 · Cited by 155 · see citing works
Self-citation
Effect of the Alzheimer amyloid fragment Aβ(25–35) on Akt/PKB kinase and survival of PC12 cells
Martı́n, D., Salinas, M., López‐Valdaliso, R., Serrano, E., Recuero, M., & Cuadrado, A. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00472.x · Cited by 140 · see citing works
Alzheimer's Disease in Down Syndrome.
Head, E., Powell, D. K., Gold, B. T., & Schmitt, F. A. (2012) · PubMed · Cited by 139 · see citing works
Self-citation
PIM1 Protein Kinase regulates PRAS40 phosphorylation and mTOR activity in FDCP1 cells
Zhang, F., Beharry, Z. M., Harris, T. E., Lilly, M. B., Smith, C. D., Mahajan, S., & Kraft, A. S. (2009) · Cancer Biology & Therapy · doi:10.4161/cbt.8.9.8210 · Cited by 139 · see citing works
Dyrk1A expression pattern supports specific roles of this kinase in the adult central nervous system
Martı́, E., Altafaj, X., Dierssen, M., de la Luna, S., Fotaki, V., Alvarez, M., Pérez-Riba, M., Ferrer, I., & Estivill, X. (2003) · Brain Research · doi:10.1016/s0006-8993(02)04069-6 · Cited by 136 · see citing works
Inhibition of Akt/mTOR Attenuates Age-Related Changes in Mesenchymal Stem Cells
Gharibi, B., Farzadi, S., Ghuman, M. S., & Hughes, F. J. (2014) · Stem Cells · doi:10.1002/stem.1709 · Cited by 134 · see citing works
Amyloid-β Toxicity and Tau Hyperphosphorylation are Linked Via RCAN1 in Alzheimer's Disease
Lloret, A., Badía, M.-C., Giraldo, E., Ermak, G., Alonso, M.-D., Pallardó, F. V., Davies, K. J. A., & Viña, J. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110890 · Cited by 133 · see citing works
Impairment of proteostasis network in Down syndrome prior to the development of Alzheimer's disease neuropathology: Redox proteomics analysis of human brain
Domenico, F. D., Coccia, R., Cocciolo, A., Murphy, M. P., Cenini, G., Head, E., Butterfield, D. A., Giorgi, A., Schininà, M. E., Mancuso, C., et al. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.04.013 · Cited by 133 · see citing works
Self-citation
The Drosophila homolog of Down's syndrome critical region 1 gene regulates learning: Implications for mental retardation
Chang, K. T., Shi, Y., & Min, K. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2536696100 · Cited by 129 · see citing works
The polyphenols resveratrol and epigallocatechin-3-gallate restore the severe impairment of mitochondria in hippocampal progenitor cells from a Down syndrome mouse model
Valenti, D., Lidia de, B. A. R. I., Rasmo, D. D., Signorile, A., Henrion‐Caude, A., Contestabile, A., & Vacca, R. A. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.03.003 · Cited by 128 · see citing works
How longevity research can lead to therapies for Alzheimer's disease: The rapamycin story
Richardson, A. G., Galván, V., Lin, A., & Oddo, S. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.12.002 · Cited by 122 · see citing works
The DSCR1 ( Adapt78 ) isoform 1 protein calcipressin 1 inhibits calcineurin and protects against acute calcium‐mediated stress damage, including transient oxidative stress
Ermak, G., Harris, C. D., & Davies, K. J. A. (2002) · The FASEB Journal · doi:10.1096/fj.01-0846com · Cited by 121 · see citing works
Mitochondrial dysfunction and tau hyperphosphorylation in Ts1Cje, a mouse model for Down syndrome
Ebrahim, A. S., Shimohata, A., Akagi, T., Yu, W., Yamaguchi, M., Murayama, M., Chui, D., Takeuchi, T., Amano, K., Subramhanya, K. H., et al. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl211 · Cited by 117 · see citing works
The Triangle of Death in Alzheimer's Disease Brain: The Aberrant Cross-Talk Among Energy Metabolism, Mammalian Target of Rapamycin Signaling, and Protein Homeostasis Revealed by Redox Proteomics
Di Domenico, F., Barone, E., Perluigi, M., & Butterfield, D. A. (2017) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6759 · Cited by 114 · see citing works
Self-citation
The role of overexpressed DYRK1A protein in the early onset of neurofibrillary degeneration in Down syndrome
Węgiel, J., Dowjat, K., Kaczmarski, W., Kuchna, I., Nowicki, K., Frackowiak, J., Mazur‐Kolecka, B., Wegiel, J., Silverman, W. P., Reisberg, ‌., et al. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0419-6 · Cited by 113 · see citing works
Abnormal APP, cholinergic and cognitive function in Ts65Dn Down's model mice
Seo, H., & Ole Isacson, A. (2005) · Experimental Neurology · doi:10.1016/j.expneurol.2004.11.017 · Cited by 112 · see citing works
Redox proteomics analysis to decipher the neurobiology of Alzheimer-like neurodegeneration: overlaps in Down's syndrome and Alzheimer's disease brain
Butterfield, D. A., Domenico, F. D., Swomley, A. M., Head, E., & Marzia Perluigi, A. (2014) · Biochemical Journal · doi:10.1042/bj20140772 · Cited by 111 · see citing works
Self-citation
O‐GlcNAcylation: A regulator of tau pathology and neurodegeneration
Gong, C., Liu, F., & Iqbal, K. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.02.011 · Cited by 111 · see citing works
Alzheimer's Disease in the Down Syndrome: An Overview of Genetics and Molecular Aspects
Gomes, F. D. C., Mattos, M. F., Goloni‐Bertollo, E. M., & Pavarino, É. C. (2021) · Neurology India · doi:10.4103/0028-3886.310062 · Cited by 102 · see citing works
Redox proteomics analysis of HNE-modified proteins in Down syndrome brain: clues for understanding the development of Alzheimer disease
Domenico, F. D., Pupo, G., Tramutola, A., Giorgi, A., Schininà, M. E., Coccia, R., Head, E., Butterfield, D. A., & Marzia Perluigi, A. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.03.027 · Cited by 98 · see citing works
Self-citation
Deregulated mTOR-mediated translation in intellectual disability.
Troca-Marín, J. A., Alves-Sampaio, A., & Montesinos, M. (2012) · Progress in neurobiology · doi:10.1016/j.pneurobio.2012.01.005 · Cited by 97 · see citing works
Dyrk1A overexpression leads to increase of 3R-tau expression and cognitive deficits in Ts65Dn down syndrome mice
Yin, X., Jin, N., Shi, J., Zhang, Y., Wu, Y., Gong, C.-X., Iqbal, K., & Liu, F. (2017) · Scientific Reports · doi:10.1038/s41598-017-00682-y · Cited by 93 · see citing works
Protein expression of BACE1, BACE2 and APP in Down syndrome brains
Cheon, M. S., Dierssen, M., Kim, S. H., & Lübec, G. (2007) · Amino Acids · doi:10.1007/s00726-007-0618-9 · Cited by 92 · see citing works
Regulation of RCAN1 Protein Activity by Dyrk1A Protein-mediated Phosphorylation
Jung, M., Park, J., Ryu, Y. S., Choi, S., Yoon, S., Kwen, M., Oh, J. Y., Song, W., & Chung, S. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.253971 · Cited by 89 · see citing works
Cardiovascular Disease and mTOR Signaling
Chong, Z. Z., Shang, Y. C., & Maiese, K. (2011) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2012.04.005 · Cited by 87 · see citing works
Phosphorylation of Tau proteins: a major event during the process of neurofibrillary degeneration. A comparative study between Alzheimer's disease and Down's syndrome
Flament, S., Delacourte, A., & Mann, D. M. A. (1990) · Brain Research · doi:10.1016/0006-8993(90)90891-e · Cited by 86 · see citing works
Tau protein degradation is catalyzed by the ATP/ubiquitin-independent 20S proteasome under normal cell conditions
Grune, T., Botzen, D., Engels, M., Voß, P., Kaiser, B., Jung, T., Grimm, S., Ermak, G., & Davies, K. J. A. (2010) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2010.05.008 · Cited by 85 · see citing works
Age-dependent dysregulation of brain amyloid precursor protein in the Ts65Dn down syndrome mouse model
Choi, J. H. K., Berger, J. D., Mazzella, M. J., Morales‐Corraliza, J., Cataldo, A. M., Nixon, R. A., Ginsberg, S. D., Levy, E., & Mathews, P. M. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06277.x · Cited by 83 · see citing works
Control of proteasomal proteolysis by mTOR
Zhao, J., Garcia, G. A., & Goldberg, A. L. (2016) · Nature · doi:10.1038/nature16472 · Cited by 79 · see citing works
Sorting Nexin 27 Regulates Aβ Production through Modulating γ-Secretase Activity
Wang, X., Huang, T., Zhao, Y., Zheng, Q., Thompson, R. C., Bu, G., Zhang, Y.-W., Hong, W., & Xu, H. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.09.037 · Cited by 77 · see citing works
Bach1 Overexpression in Down Syndrome Correlates with the Alteration of the HO-1/BVR-A System: Insights for Transition to Alzheimer's Disease
Di Domenico, F., Pupo, G., Mancuso, C., Barone, E., Paolini, F., Arena, A., Blarzino, C., Schmitt, F. A., Head, E., Butterfield, D. A., et al. (2015) · Journal of Alzheimer’s Disease · doi:10.3233/jad-141254 · Cited by 75 · see citing works
Self-citation
Neuropathological Criteria for the Diagnosis of Alzheimer’s Disease
Markesbery, W. R. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00064-x · Cited by 74 · see citing works
Modulation of Aβ generation by small ubiquitin-like modifiers does not require conjugation to target proteins
Dorval, V., Mazzella, M. J., Mathews, P. M., Hay, R. T., & Fraser, P. E. (2007) · Biochemical Journal · doi:10.1042/bj20061451 · Cited by 70 · see citing works
Oxidative and calcium stress regulate DSCR1 (Adapt78/MCIP1) protein
Lin, H., Michtalik, H. J., Zhang, S., Andersen, T. T., Riper, D. A. V., Davies, K. J. A., Ermak, G., Petti, L. M., Nachod, S., Narayan, A., et al. (2003) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(03)00358-7 · Cited by 70 · see citing works
mTOR Hyperactivation in Down Syndrome Hippocampus Appears Early During Development
Iyer, A. M., van Scheppingen, J., Milenkovic, I., Anink, J. J., Adle-Biassette, H., Kovacs, G. G., & Aronica, E. (2014) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000083 · Cited by 69 · see citing works
Chronic Expression of RCAN1-1L Protein Induces Mitochondrial Autophagy and Metabolic Shift from Oxidative Phosphorylation to Glycolysis in Neuronal Cells
Ermak, G., Sojitra, S., Yin, F., Cadenas, E., Cuervo, A. M., & Davies, K. J. A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.305342 · Cited by 69 · see citing works
Targeting mTOR to reduce Alzheimer-related cognitive decline: from current hits to future therapies.
Tramutola, A., Lanzillotta, C., & Di Domenico, F. (2017) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2017.1244482 · Cited by 69 · see citing works
Self-citation
Role of Tau Protein in Neuronal Damage in Alzheimer's Disease and Down Syndrome
Cárdenas, A. M., Ardiles, Á. O., Barraza, N., Báez‐Matus, X., & Caviedes, P. A. (2012) · Archives of Medical Research · doi:10.1016/j.arcmed.2012.10.012 · Cited by 63 · see citing works
RCAN1 (DSCR1 or Adapt78)* stimulates expression of GSK‐3β
Ermak, G., Harris, C. D., Battocchio, D., & Davies, K. J. A. (2006) · FEBS Journal · doi:10.1111/j.1742-4658.2006.05217.x · Cited by 58 · see citing works
NFATs and Alzheimer's Disease.
Abdul, H. M., Furman, J. L., Sama, M. A., Mathis, D. M., & Norris, C. M. (2010) · PubMed · Cited by 57 · see citing works
Altered regulation of tau phosphorylation in a mouse model of down syndrome aging
Sheppard, O., Plattner, F., Rubin, A. N., Slender, A., Linehan, J. M., Brandner, S., Tybulewicz, V. L. J., Fisher, E., & Wiseman, F. K. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.06.025 · Cited by 57 · see citing works
Polyubiquitinylation Profile in Down Syndrome Brain Before and After the Development of Alzheimer Neuropathology
Tramutola, A., Di Domenico, F., Barone, E., Arena, A., Giorgi, A., di Francesco, L., Schininà, M. E., Coccia, R., Head, E., Butterfield, D. A., et al. (2017) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6686 · Cited by 49 · see citing works
Self-citation
Cathepsin D as a therapeutic target in Alzheimer’s disease
Domenico, F. D., Tramutola, A., & Perluigi, M. (2016) · Expert opinion on therapeutic targets · doi:10.1080/14728222.2016.1252334 · Cited by 48 · see citing works
Self-citation
Decrease of Protein Phosphatase 2A and its Association with Accumulation and Hyperphosphorylation of Tau in Down Syndrome
Liang, Z., Liu, F., Iqbal, K., Grundke, I., Węgiel, J., & Gong, C. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-13307 · Cited by 43 · see citing works
Abnormal Expression of Synaptic Proteins and Neurotrophin-3 in the Down Syndrome Mouse Model Ts65Dn
Pollonini, G., Gao, V., Rabe, A., Palminiello, S., Albertini, G., & Alberini, C. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.07.025 · Cited by 42 · see citing works
The chromosome 21 transcription factor ETS2 transactivates the β-APP promoter: implications for Down syndrome
Wolvetang, E. J., Bradfield, O., Tymms, M. J., Zavarsek, S., Hatzistavrou, T., Kola, I., & Hertzog, P. J. (2003) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(03)00121-0 · Cited by 42 · see citing works
Rapamycin Allosterically Inhibits the Proteasome
Osmulski, P. A., & Gaczynska, M. E. (2013) · Molecular Pharmacology · doi:10.1124/mol.112.083873 · Cited by 41 · see citing works
Activation of p53 in Down Syndrome and in the Ts65Dn mouse brain is associated with a pro-apoptotic phenotype
Tramutola, A., Pupo, G., Di Domenico, F., Barone, E., Arena, A., Lanzillotta, C., Broekaart, D., Blarzino, C., Head, E., Butterfield, D. A., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-151105 · Cited by 40 · see citing works
Self-citation
Reduction of calcineurin activity in brain by antisense oligonucleotides leads to persistent phosphorylation of tau protein at Thr181 and Thr231.
Garver, T. D., Kincaid, R. L., Conn, R. A., & Billingsley, M. L. (1999) · PubMed · Cited by 40 · see citing works
Increased Mammalian Target of Rapamycin Signaling Contributes to the Accumulation of Protein Oxidative Damage in a Mouse Model of Down's Syndrome
Tramutola, A., Lanzillotta, C., Arena, A., Barone, E., Marzia Perluigi, A., & Domenico, F. D. (2015) · Neurodegenerative Diseases · doi:10.1159/000441419 · Cited by 39 · see citing works
Self-citation
The wheat germ agglutinin‐fractionated proteome of subjects with Alzheimer's disease and mild cognitive impairment hippocampus and inferior parietal lobule: Implications for disease pathogenesis and progression
Domenico, F. D., Owen, J. B., Rukhsana Sultana, A., Robinson, R. A. S., Marzia Perluigi, A., Cini, C., Cai, J., Pierce, W. M. J., & Butterfield, D. A. (2010) · Journal of Neuroscience Research · doi:10.1002/jnr.22528 · Cited by 38 · see citing works
Self-citation
Parallel Compensatory and Pathological Events Associated with Tau Pathology in Middle Aged Individuals with Down Syndrome
Head, E., Lott, I. T., Hof, P. R., Bouras, C., Su, J., Kim, R., Haier, R. J., & Cotman, C. W. (2003) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/62.9.917 · Cited by 36 · see citing works
Self-citation
Leptin, a mediator of cardiac damage associated with obesity
Martínez‐Martínez, E., Jurado-López, R., Cervantes-Escalera, P., Cachofeiro, V., & Miana, M. (2014) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2013-0060 · Cited by 27 · see citing works
β -Secretases, Alzheimer’s Disease, and Down Syndrome
Webb, R. L., & Murphy, M. P. (2012) · Current Gerontology and Geriatrics Research · doi:10.1155/2012/362839 · Cited by 24 · see citing works
Reduction of Calcineurin Activity in Brain by Antisense Oligonucleotides Leads to Persistent Phosphorylation of τ Protein at Thr181 and Thr231
Garver, T. D., Kincaid, R. L., Conn, R. A., & Billingsley, M. L. (1999) · Molecular Pharmacology · doi:10.1016/s0026-895x(24)23024-8 · Cited by 23 · see citing works
The Extended Tau Haplotype and the Age of Onset of Dementia in Down Syndrome
Jones, E. L., Margallo‐Lana, M., Prasher, V. P., & Ballard, C. G. (2008) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000152044 · Cited by 21 · see citing works
SET translocation is associated with increase in caspase cleaved amyloid precursor protein in CA1 of Alzheimer and Down syndrome patients
Facchinetti, P., Dorard, E., Contremoulins, V., Gaillard, M., Déglon, N., Sazdovitch, V., Guihenneuc‐Jouyaux, C., Brouillet, E., Duyckaerts, C. J., & Allinquant, B. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.08.039 · Cited by 15 · see citing works
Insights from Mouse Models to Understand Neurodegeneration in Down Syndrome
Fillat, C., Dierssen, M., de Lagrán, M. M., & Altafaj, X. (2010) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152710791556159 · Cited by 11 · see citing works
Increases of SET level and translocation are correlated with tau hyperphosphorylation at ser202/thr205 in CA1 of Ts65Dn mice
Dorard, E., Gorisse-Hussonnois, L., Guihenneuc‐Jouyaux, C., Albac, C., Potier, M., & Allinquant, B. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.06.010 · Cited by 5 · see citing works

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Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
Jomova, K., Raptova, R., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03562-9 · Cited by 2,638 · see citing works
Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease
Butterfield, D. A., & Halliwell, B. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0132-6 · Cited by 1,954 · see citing works
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Multicomponent peptide assemblies
Raymond, D. M., & Nilsson, B. L. (2018) · Chemical Society Reviews · doi:10.1039/c8cs00115d · Cited by 348 · see citing works
Oxidative damage in neurodegeneration: roles in the pathogenesis and progression of Alzheimer disease
Marzia Perluigi, A., Domenico, F. D., & Butterfield, D. A. (2023) · Physiological Reviews · doi:10.1152/physrev.00030.2022 · Cited by 306 · see citing works
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Mammalian/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration
Querfurth, H., & Lee, H.-K. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00428-5 · Cited by 288 · see citing works
Metabolic Dysregulation Contributes to the Progression of Alzheimer’s Disease
Yan, X., Hu, Y., Wang, B., Wang, S., & Zhang, X. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.530219 · Cited by 217 · see citing works
Apolipoprotein E and oxidative stress in brain with relevance to Alzheimer's disease
Butterfield, D. A., & Mattson, M. P. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104795 · Cited by 187 · see citing works
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Trisomy 21 dysregulates T cell lineages toward an autoimmunity-prone state associated with interferon hyperactivity
Araya, P., Waugh, K. A., Sullivan, K. D., Núñez, N. G., Roselli, E., Smith, K. P., Granrath, R. E., Rachubinski, A. L., Enriquez Estrada, B., Butcher, E. T., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1908129116 · Cited by 179 · see citing works
Melatonin and Autophagy in Aging-Related Neurodegenerative Diseases
Luo, F., Sandhu, A. F., Rungratanawanich, W., Williams, G. E., Akbar, M. D., Zhou, S., Song, B., & Wang, X. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197174 · Cited by 158 · see citing works
mTOR hyperactivation in Down Syndrome underlies deficits in autophagy induction, autophagosome formation, and mitophagy
Bordi, M., Darji, S., Sato, Y., Mellén, M., Berg, M. J., Kumar, A., Jiang, Y., & Nixon, R. A. (2019) · Cell Death & Disease · doi:10.1038/s41419-019-1752-5 · Cited by 124 · see citing works
mTOR in Alzheimer disease and its earlier stages: Links to oxidative damage in the progression of this dementing disorder
Marzia Perluigi, A., Domenico, F. D., Barone, E., & Butterfield, D. A. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.04.025 · Cited by 121 · see citing works
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AMPK: A bridge between diabetes mellitus and Alzheimer's disease
Chen, M., Huang, N., Liu, J., Huang, J., Shi, J., & Jin, F. J. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.113043 · Cited by 118 · see citing works
Amyloid-beta and tau protein beyond Alzheimer’s disease
Abyadeh, M., Gupta, V., Paulo, J. A., Mahmoudabad, A. G., Shadfar, S., Mirshahvaladi, S., Gupta, V. B., Nguyen, C. T. O., Finkelstein, D. I., You, Y., et al. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.386406 · Cited by 121 · see citing works
Altered Metabolism in Alzheimer Disease Brain: Role of Oxidative Stress
Rummel, N. G., & Butterfield, D. A. (2021) · Antioxidants and Redox Signaling · doi:10.1089/ars.2021.0177 · Cited by 105 · see citing works
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Intranasal rapamycin ameliorates Alzheimer-like cognitive decline in a mouse model of Down syndrome
Tramutola, A., Lanzillotta, C., Barone, E., Arena, A., Zuliani, I., Mosca, L., Blarzino, C., Butterfield, D. A., Marzia Perluigi, A., & Domenico, F. D. (2018) · Translational Neurodegeneration · doi:10.1186/s40035-018-0133-9 · Cited by 101 · see citing works
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Role of insulin receptor substance-1 modulating PI3K/Akt insulin signaling pathway in Alzheimer’s disease
Zheng, M., & Wang, P. (2021) · 3 Biotech · doi:10.1007/s13205-021-02738-3 · Cited by 98 · see citing works
Down syndrome: Neurobiological alterations and therapeutic targets
Vacca, R. A., Bawari, S., Valenti, D., Tewari, D., Nabavi, S. F., Shirooie, S., Sah, A. N., Volpicella, M., Braidy, N., & Nabavi, S. M. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.01.001 · Cited by 90 · see citing works
Down syndrome and Alzheimer's disease: common molecular traits beyond the amyloid precursor protein
Gómez, W., Morales, R., Maracaja‐Coutinho, V., Parra, V., & Nassif, M. (2020) · Aging · doi:10.18632/aging.102677 · Cited by 87 · see citing works
Iron Exposure and the Cellular Mechanisms Linked to Neuron Degeneration in Adult Mice
Li, L.-B., Chai, R., Zhang, S., Xu, S., Zhang, Y., Li, H., Fan, Y., & Guo, C. (2019) · Cells · doi:10.3390/cells8020198 · Cited by 83 · see citing works
Proteomics Study of Peripheral Blood Mononuclear Cells in Down Syndrome Children
Lanzillotta, C., Greco, V., Valentini, D., Villani, A., Folgiero, V., Caforio, M., Locatelli, F., Pagnotta, S. E., Barone, E., Urbani, A., et al. (2020) · Antioxidants · doi:10.3390/antiox9111112 · Cited by 85 · see citing works
Accelerated bio‐cognitive aging in Down syndrome: State of the art and possible deceleration strategies
Franceschi, C., Garagnani, P., Gensous, N., Bacalini, M. G., Conte, M., & Salvioli, S. (2019) · Aging Cell · doi:10.1111/acel.12903 · Cited by 80 · see citing works
Restoration of aberrant mTOR signaling by intranasal rapamycin reduces oxidative damage: Focus on HNE-modified proteins in a mouse model of down syndrome
Domenico, F. D., Tramutola, A., Barone, E., Lanzillotta, C., Defever, O., Arena, A., Zuliani, I., Foppoli, C., Iavarone, F., Vincenzoni, F., et al. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101162 · Cited by 69 · see citing works
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Autophagy in Alzheimer's disease and promising modulatory effects of herbal medicine
Zeng, Q., Siu, W. S., Li, L., Yu, J., Liang, S., Cao, M., Ma, M., & Wu, Z. (2019) · Experimental Gerontology · doi:10.1016/j.exger.2019.01.027 · Cited by 64 · see citing works
mTOR signaling as a molecular target for the alleviation of Alzheimer's disease pathogenesis
Rapaka, D., Bitra, V. R., Challa, S. R., & Adiukwu, P. C. (2022) · Neurochemistry International · doi:10.1016/j.neuint.2022.105311 · Cited by 65 · see citing works
Perspectives on Oxidative Stress in Alzheimer’s Disease and Predictions of Future Research Emphases
Butterfield, D. A. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-179912 · Cited by 57 · see citing works
Self-citation
The 5-HT6 receptor interactome: New insight in receptor signaling and its impact on brain physiology and pathologies
Chaumont‐Dubel, S., Dupuy, V., Bockaert, J., Bécamel, C., & Marin, P. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.107839 · Cited by 58 · see citing works
Aerobic Exercise Improves Synaptic-Related Proteins of Diabetic Rats by Inhibiting FOXO1/NF-κB/NLRP3 Inflammatory Signaling Pathway and Ameliorating PI3K/Akt Insulin Signaling Pathway
Wang, Q., Hu, J., Liu, Y., Li, J., Liu, B., Li, M., & Lou, S. (2019) · Journal of Molecular Neuroscience · doi:10.1007/s12031-019-01302-2 · Cited by 53 · see citing works
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Stanciu, G. D., Rusu, R. N., Bild, V., Filipiuc, L. E., Tamba, B.-I., & Ababei, D. C. (2021) · Biomedicines · doi:10.3390/biomedicines9050576 · Cited by 47 · see citing works
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Lanzillotta, C., Tramutola, A., Di Giacomo, G., Marini, F., Butterfield, D. A., Di Domenico, F., Perluigi, M., & Barone, E. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.01.042 · Cited by 47 · see citing works
Self-citation
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Lanzillotta, C., Zuliani, I., Tramutola, A., Barone, E., Blarzino, C., Folgiero, V., Caforio, M., Valentini, D., Villani, A., Locatelli, F., et al. (2020) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101892 · Cited by 44 · see citing works
Self-citation
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Mollo, N., Cicatiello, R., Aurilia, M., Scognamiglio, R., Genesio, R., Charalambous, M., Paladino, S., Conti, A. M. F., Nitsch, L., & Izzo, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093134 · Cited by 39 · see citing works
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Moreno, M. D. M. M., Brault, V., Birling, M., Pavlovic, G., & Hérault, Y. (2020) · Progress in brain research · doi:10.1016/bs.pbr.2019.08.001 · Cited by 32 · see citing works
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Shirooie, S., Nabavi, S. F., Dehpour, A. R., Belwal, T., Habtemariam, S., Argüelles, S., Sureda, A., Daglia, M., Tomczyk, M., Sobarzo‐Sánchez, E., et al. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.07.004 · Cited by 37 · see citing works
Dual-acting agents for improving cognition and real-world function in Alzheimer’s disease: Focus on 5-HT6 and D3 receptors as hubs
Millan, M. J., Dekeyne, A., Gobert, A., Brocco, M., la Cour, C. M., Ortuno, J., Watson, D. J., & Fone, K. C. F. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108099 · Cited by 37 · see citing works
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Lanzillotta, C., & Domenico, F. D. (2021) · Biomolecules · doi:10.3390/biom11020266 · Cited by 35 · see citing works
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Rueda Revilla, N., & Martínez-Cué, C. (2020) · Antioxidants · doi:10.3390/antiox9080692 · Cited by 35 · see citing works
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Guest, F. L., Rahmoune, H., & Guest, P. C. (2020) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-030-42667-5_8 · Cited by 34 · see citing works
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Sheng, C., Xiaojun, L., Hai-zhen, W., Fu, L., Shaozhen, L., Su, Z., Weiliang, H., Chunhong, J., Wang, Y., Wu, F., et al. (2018) · Life Sciences · doi:10.1016/j.lfs.2018.12.050 · Cited by 31 · see citing works
Ubiquitin carboxyl-terminal hydrolase L-1 in brain: Focus on its oxidative/nitrosative modification and role in brains of subjects with Alzheimer disease and mild cognitive impairment
Butterfield, D. A. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.10.036 · Cited by 30 · see citing works
Self-citation
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Mollo, N., Esposito, M., Aurilia, M., Scognamiglio, R., Accarino, R., Bonfiglio, F., Cicatiello, R., Charalambous, M., Procaccini, C., Micillo, T., et al. (2021) · Biology · doi:10.3390/biology10070609 · Cited by 29 · see citing works
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Zuliani, I., Lanzillotta, C., Tramutola, A., Francioso, A., Pagnotta, S. E., Barone, E., Marzia Perluigi, A., & Domenico, F. D. (2020) · Neurotherapeutics · doi:10.1007/s13311-020-00978-4 · Cited by 29 · see citing works
Self-citation
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Martínez‐Cué, C., & Rueda, N. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186906 · Cited by 26 · see citing works
Molecular mechanisms of sex hormones in the development and progression of Alzheimer's disease
Radaghdam, S., Karamad, V., Nourazarian, A., Shademan, B., Khaki‐Khatibi, F., & Nikanfar, M. (2021) · Neuroscience Letters · doi:10.1016/j.neulet.2021.136221 · Cited by 28 · see citing works
Association Between Plasma Metabolites and Psychometric Scores Among Children With Developmental Disabilities: Investigating Sex-Differences
Sotelo-Orozco, J., Abbeduto, L., Hertz‐Picciotto, I., & Slupsky, C. M. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.579538 · Cited by 25 · see citing works
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Li, W., Su, D., Zhai, Q., Chi, H., She, X., Gao, X., Wang, K., Yang, H., Wang, R., & Cui, B. (2019) · Environmental Research · doi:10.1016/j.envres.2019.108537 · Cited by 24 · see citing works
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Smith‐Sonneborn, J. (2019) · Current Aging Science · doi:10.2174/1874609812666190620124324 · Cited by 23 · see citing works
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Besterman, A. D., Althoff, T., Elfferich, P., Gutierrez-Mejia, I., Sadik, J., Bernstein, J. A., van Ierland, Y., Kattentidt‐Mouravieva, A. A., Nellist, M. D., Abramson, J., et al. (2021) · PLoS Genetics · doi:10.1371/journal.pgen.1009651 · Cited by 22 · see citing works
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Domenico, F. D., Lanzillotta, C., & Marzia Perluigi, A. (2024) · FEBS Letters · doi:10.1002/1873-3468.14840 · Cited by 22 · see citing works
Whey protein powder with milk fat globule membrane attenuates Alzheimer's disease pathology in 3×Tg-AD mice by modulating neuroinflammation through the peroxisome proliferator-activated receptor γ signaling pathway
Li, Y., Zhang, Z.-H., Huang, S. L., Yue, Z., Yin, X., Feng, Z., Zhang, X., & Song, G.-L. (2023) · Journal of Dairy Science · doi:10.3168/jds.2023-23254 · Cited by 21 · see citing works
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Zamponi, E., & Helguera, P. R. (2019) · Developmental Neurobiology · doi:10.1002/dneu.22673 · Cited by 20 · see citing works
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Chiang, A. C. A., Fowler, S., Savjani, R. R., Hilsenbeck, S. G., Wallace, C. E., Cirrito, J. R., Das, P., & Jankowsky, J. L. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20171484 · Cited by 18 · see citing works
Down Syndrome, Ageing and Epigenetics
Gensous, N., Franceschi, C., Salvioli, S., Garagnani, P., & Bacalini, M. G. (2019) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-981-13-3681-2_7 · Cited by 19 · see citing works
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Kaur, G., Gauthier, S. A., Pérez‐González, R., Pawlik, M., Singh, A. B., Cosby, B., Mohan, P. S., Smiley, J. F., & Levy, E. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.08.025 · Cited by 17 · see citing works
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Cho, C., Michailidis, V., & Martin, L. J. (2018) · Neurobiology of Pain · doi:10.1016/j.ynpai.2018.03.002 · Cited by 15 · see citing works
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Butterfield, D. A. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.08.035 · Cited by 13 · see citing works
Self-citation
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Cao, Y., Liu, B., Xu, W., Wang, L., Shi, F.-X., Li, N., Lei, Y., Wang, J., Tian, Q., & Zhou, X. (2020) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2020.06.002 · Cited by 13 · see citing works
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Yang, C., Li, X., Zhang, L., Li, Y., Li, L., & Zhang, L. (2019) · Journal of Natural Medicines · doi:10.1007/s11418-019-01318-3 · Cited by 13 · see citing works
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Elangovan, A., Babu, H. W. S., Iyer, M., Gopalakrishnan, A. V., & Vellingiri, B. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101930 · Cited by 11 · see citing works
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Sun, Y., Liu, C., & He, L. (2024) · Antioxidants and Redox Signaling · doi:10.1089/ars.2023.0455 · Cited by 11 · see citing works
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Zufferey, V., Barve, A., Parietti, E., Belinga, L. N., Bringaud, A., Varisco, Y., Fabbri, K., Capotosti, F., Bezzi, P., Déglon, N., et al. (2025) · Translational Neurodegeneration · doi:10.1186/s40035-025-00474-9 · Cited by 10 · see citing works
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Park, S., Park, M., & Lee, H. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118472 · Cited by 10 · see citing works
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Sharallah, O. A., Poddar, N. K., & Alwadan, O. A. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102394 · Cited by 7 · see citing works
The mTOR pathway: a common link between Alzheimer's disease and Down Syndrome
Wohlfert, A. J., Phares, J., & Granholm, A.-C. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13206183 · Cited by 6 · see citing works
Brain insulin resistance: an early risk factor for Alzheimer's disease development in Down syndrome
Barone, E. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.317979 · Cited by 6 · see citing works
Current insights and prospects for the pathogenesis and treatment of clinical manifestations associated with Down syndrome through neurotransmitter, inflammatory, and oxidative stress pathways
Alasmari, F. F., Ahmad, A., Alsanea, S., Hammad, A. M., & Al-Qerem, W. A. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1592277 · Cited by 5 · see citing works
Down syndrome: From development to adult life to Alzheimer disease
Butterfield, D. A., & Marzia Perluigi, A. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.10.374 · Cited by 5 · see citing works
Self-citation
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Zhang, S., Wang, T., Gu, X. F., Zheng, R., Ding, N., Yang, J., & Zhang, M. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251400667 · Cited by 5 · see citing works
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Azodi, M. Z., Rezaei–Tavirani, M., Tavirani, M. R., & Rostami‐Nejad, M. (2021) · Basic and Clinical Neuroscience Journal · doi:10.32598/bcn.12.1.941.6 · Cited by 4 · see citing works
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SHARMA, A. K., Devi, S., Mannan, A., Kumar, M., & Singh, T. G. (2024) · Current Signal Transduction Therapy · doi:10.2174/0115743624267214241016103515 · Cited by 4 · see citing works
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Corraliza-Gómez, M. (2021) · doi:10.35376/10324/51889 · Cited by 4 · see citing works
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Granholm, A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26168092 · Cited by 3 · see citing works
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Donovan, M. G., Chillamcherla, S., Estrada, B. A. E., Worek, K. R., Sundararajan, Z., Barstch, K. W., Sullivan, K. D., Galbraith, M. D., Rachubinski, A. L., & Espinosa, J. M. (2026) · Nature Communications · doi:10.1038/s41467-026-72946-z · Cited by 3 · see citing works
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Zhang, L., Fernandez-Kim, S.-O., Beckett, T. L., Niedowicz, D. M., Köhler, K., Dasuri, K., Bruce‐Keller, A. J., Murphy, M. P., & Keller, J. N. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2019.04.013 · Cited by 3 · see citing works
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Barros‐Santos, B., Campos‐Marques, C., Salvador, A. F., & Silva, J. M. (2025) · Brain Organoid and Systems Neuroscience Journal · doi:10.1016/j.bosn.2025.04.006 · Cited by 2 · see citing works
A seven-year longitudinal study of the Alzheimer’s disease blood metabolomePreprint
Marella, B., Weinisch, P., Bless, J. J., Risacher, S. L., Blach, C., Karu, N., Kalecký, K., Wang, T., Huynh, K., Kueider‐Paisley, A., et al. (2025) · medRxiv · doi:10.64898/2025.12.05.25341709 · Cited by 2 · see citing works
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Cipriano, G. L., Floramo, A., Argento, V., Oddo, S., & Artimagnella, O. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27010455 · Cited by 1 · see citing works
Oxidative stress and mTOR in Down syndrome brain: Link to Alzheimer's dysmetabolism, neuropathology, and possible therapies
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Self-citation
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O’Brien, K., & Blair, P. (2021) · Springer eBooks · doi:10.1007/978-3-030-78559-8_9 · Cited by 1 · see citing works
Modeling Taupathies in Zebrafish (Danio rerio)
Kotova, M. M., Kolesnikova, T. O., & Kalueff, A. V. (2023) · Российский физиологический журнал им И М Сеченова · doi:10.31857/s0869813923110067 · Cited by 1 · see citing works
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Wang, B., Dong, R., Xu, L., Sun, X., Chen, H., Zhou, J., Li, X., Wang, M., & Bi, Y. (2019) · Cognitive and Behavioral Neurology · doi:10.1097/wnn.0000000000000205
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Jing, S., Liu, C., Lin, H., Zhang, X., Wang, F., Gao, J., Sun, J., Chen, J., Wang, C., & Li, H. (2020) · Natural Product Communications · doi:10.1177/1934578x19900687
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Besterman, A. D., Althoff, T., Elfferich, P., Sonneveld, M., Gutierrez-Mejia, I., Sadik, J., Bernstein, J. A., Kattentidt‐Mouravieva, A. A., van Ierland, Y., Nellist, M. D., et al. (2021) · Molecular Genetics and Metabolism · doi:10.1016/s1096-7192(21)00247-x
Modeling Tauopathies in Zebrafish (Danio rerio)
Kotova, M. M., Kolesnikova, T. O., & Kalueff, A. V. (2023) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093023060133
Targeting mTOR restores tau-induced metabolic, mitochondrial, and cognitive deficits in a tauopathy mouse modelPreprint
Tang, Z., Guo, M., Ding, Y., Wen, Y., Li, B., Xiao, Y., Ni, R., Guan, Z.-Z., & Qi, X. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.11.24.625068 · Cited by 1 · see citing works
The N-degron pathway modulates autophagosome biogenesis in selective autophagy via the p62-TRAF6-VPS34 circuitPreprint
Ji, C. H., Kim, S., Lee, S. H., Kim, D. H., Jo, J. S., Lee, M. J., Lee, S. J., Kwon, S. C., Bae, J., Jung, C. H., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-8953038/v1
Le récepteur 5-ht6 de la sérotonine : caractérisation de son expression et de ses rôles neurodéveloppementaux
Dupuy, V. (2021) · theses.fr (ABES) · doi:10.70675/1d3fd850zcfc7z46d8z8a48z1d2f5b03ffd2
Autophagy and molecular chaperones in neurodegenerative disease
Upadhyay, R., Rangappa, N., Sevanan, M., & Chinnathambi, S. (2026) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2026.06.003
Metformin improves mitophagy-related pathways and mitochondrial-lysosomal homeostasis in chromosome 21 trisomic fibroblasts
Mollo, N., NATALE, R., D'Ariano, M., Coppola, S., Meglio, D. D., Limone, A., Calı̀, G., D’Agostino, C., Pastore, N., Sarnataro, D., et al. (2026) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-026-06355-2
Demenz: Alzheimerkrankheit
O’Brien, K., & Blair, P. (2026) · Springer eBooks · doi:10.1007/978-3-032-14521-5_9

Oxidative Stress and mTOR Activation in Down Syndrome Brain: Roles in Aβ42 and Tau Neuropathology and Transition to Alzheimer Disease-Like Dementia
Butterfield, D. A., Domenico, F. D., Tramutola, A., Head, E., & Marzia Perluigi, A. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.10.099 · Cited by 3 · see citing works
Self-citation
The mTOR pathway: a common link between Alzheimer's disease and Down Syndrome
Wohlfert, A. J., Phares, J., & Granholm, A.-C. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13206183 · Cited by 6 · see citing works
Neuropathological role of PI3K/Akt/mTOR axis in Down syndrome brain
Perluigi, M., Pupo, G., Tramutola, A., Cini, C., Coccia, R., Barone, E., Head, E., Butterfield, D. A., & Di Domenico, F. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.04.007 · Cited by 155 · see citing works
Self-citation
The mTOR Pathway and Its Relationship with Alzheimer's Disease
Zhong, L. (2010) · Zhongguo bijiao yixue zazhi
Pathological role of PI3K/AKT/mTOR signaling pathway in Down Syndrome brain
Pupo, G., Tramutola, A., Foppoli, C., & Domenico, F. D. (2013) · IRIS Research product catalog (Sapienza University of Rome)
Self-citation

Authors: Di Domenico, F., Tramutola, A., Foppoli, C., Head, E., Perluigi, M., & Butterfield, D. A.
Affiliations: Sapienza University of Rome (IT)
University of Kentucky (US)
Corresponding author: Butterfield, D. Allan
ORCID: Tramutola, Antonella
Foppoli, Cesira
Head, Elizabeth
Butterfield, D. Allan
Venue: Free Radical Biology and Medicine
Publisher: Elsevier BV
Published: 2018-01
Volume: 114
Pages: 94-101
ISSN: 0891-5849 (ISSN-L)
DOI: 10.1016/j.freeradbiomed.2017.08.009
PMC: PMC5748251
OpenAlex: W2744136361
Cited by: 89
References: 127
Citations by year: 2026: 6 · 2025: 7 · 2024: 6 · 2023: 7 · 2022: 1 · 2021: 18 · 2020: 17 · 2019: 17 · 2018: 9 · 2017: 1
FWCI: 1.48
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Free Radical Biology and Medicine (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
Funders: Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD064993)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: mTOR signaling, Down syndrome, Alzheimer's disease, amyloid-beta, tau hyperphosphorylation, neurofibrillary tangles, amyloid plaques, oxidative stress, mitochondrial dysfunction, autophagy, proteostasis, neurodegeneration, cognitive decline
MeSH terms: Neuropathology, Alzheimer Disease, Animals, Humans, Signal Transduction, Amyloid beta-Peptides, tau Proteins, TOR Serine-Threonine Kinases

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mTOR in Down syndrome: Role in Aß and tau neuropathology and transition to Alzheimer disease-like dementia

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