Molecular Mechanism for Age-Related Memory Loss: The Histone-Binding Protein RbAp48

Pavlopoulos, Elias; Jones, Sidonie; Kosmidis, Stylianos; Close, Maggie; Kim, Carla; Kovalerchik, Olga; Small, Scott A.; Kandel, Eric R.

doi:10.1126/scitranslmed.3006373

Cited by 109Memory and Neural MechanismsNeurogenesis and neuroplasticity mechanismsGenomics and Chromatin Dynamics

Molecular Mechanism for Age-Related Memory Loss: The Histone-Binding Protein RbAp48

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Pavlopoulos, Elias, Jones, Sidonie, Kosmidis, Stylianos, Close, Maggie, Kim, Carla, Kovalerchik, Olga, Small, Scott A., Kandel, Eric R.·2013·Science Translational Medicine

DOI 10.1126/scitranslmed.3006373PMC PMC4940031

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Abstract

A histone-binding protein that declines with age in the human dentate gyrus can reverse age-related memory deficits in mice.

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BDNF plays roles in plasticity and cognitive improvement.
“BDNF plays roles in plasticity and cognitive improvement.”
From 2-Deoxyglucose drives plasticity via an adaptive ER stress-ATF4 pathway and elicits stroke recovery and Alzheimer’s resilience (2023) · cites this paper as [27]
The Results section on up-regulating RbAp48 reports improved memory in aged mice, and the Discussion attributes that improvement to RbAp48-related mechanisms. Searches for “BDNF” and “brain-derived neurotrophic factor” found no passage in our copy connecting BDNF to plasticity or cognitive improvement; the paper’s findings about RbAp48 do not establish the claim about BDNF. (LLM, conf=0.75)
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“Postmortem studies have suggested that the entorhinal cortex (EC) as well as the CA1 subregion and the subiculum are the hippocampal subregions that are most affected by AD (2, 3), whereas the dentate gyrus (DG) and CA3 are relatively preserved (2, 4, 5).”
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Flagged first, then by citations

Research works printed but not linked: 43

[1]Small SA Schobel SA Buxton RB Witter MP Barnes CA A pathophysiological framework of hippocampal dysfunction in ageing and disease Nat Rev Neurosci 12 585 601 2011 21897434 PMC3312472
[4]Thal DR Rüb U Orantes M Braak H Phases of Aβ-deposition in the human brain and its relevance for the development of AD Neurology 58 1791 1800 2002 12084879
[5]West MJ Regionally specific loss of neurons in the aging human hippocampus Neurobiol Aging 14 287 293 1993 8367010
[6]Small SA Perera GM DeLaPaz R Mayeux R Stern Y Differential regional dysfunction of the hippocampal formation among elderly with memory decline and Alzheimer’s disease Ann Neurol 45 466 472 1999 10211471
[8]Moreno H Hua F Brown T Small S Longitudinal mapping of mouse cerebral blood volume with MRI NMR Biomed 19 535 543 2006 16552789
[9]Moreno H Wu WE Lee T Brickman A Mayeux R Brown TR Small SA Imaging the Aβ-related neurotoxicity of Alzheimer disease Arch Neurol 64 1467 1477 2007 17923630
[10]Small SA Chawla MK Buonocore M Rapp PR Barnes CA Imaging correlates of brain function in monkeys and rats isolates a hippocampal subregion differentially vulnerable to aging Proc Natl Acad Sci USA 101 7181 7186 2004 15118105 PMC406486
[11]Toner CK Pirogovsky E Kirwan CB Gilbert PE Visual object pattern separation deficits in nondemented older adults Learn Mem 16 338 342 2009 19403797
[12]Yassa MA Lacy JW Stark SM Albert MS Gallagher M Stark CE Pattern separation deficits associated with increased hippocampal CA3 and dentate gyrus activity in nondemented older adults Hippocampus 21 968 979 2011 20865732 PMC3010452
[13]Stark SM Yassa MA Stark CE Individual differences in spatial pattern separation performance associated with healthy aging in humans Learn Mem 17 284 288 2010 20495062 PMC2884287
[14]Brickman AM Stern Y Small SA Hippocampal subregions differentially associate with standardized memory tests Hippocampus 21 923 928 2011 20824727 PMC3008756
[15]Lewandowski NM Small SA Brain microarray: Finding needles in molecular haystacks J Neurosci 25 10341 10346 2005 16280569 PMC6725820
[16]Small SA Kent K Pierce A Leung C Kang MS Okada H Honig L Vonsattel JP Kim TW Model-guided microarray implicates the retromer complex in Alzheimer’s disease Ann Neurol 58 909 919 2005 16315276
[17]Zhang Q Vo N Goodman RH Histone binding protein RbAp48 interacts with a complex of CREB binding protein and phosphorylated CREB Mol Cell Biol 20 4970 4978 2000 10866654 PMC85947
[18]Alarcón JM Malleret G Touzani K Vronskaya S Ishii S Kandel ER Barco A Chromatin acetylation, memory, and LTP are impaired in CBP+/− mice: A model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration Neuron 42 947 959 2004 15207239
[19]Korzus E Rosenfeld MG Mayford M CBP histone acetyltransferase activity is a critical component of memory consolidation Neuron 42 961 972 2004 15207240 PMC8048715
[20]Vecsey CG Hawk JD Lattal KM Stein JM Fabian SA Attner MA Cabrera SM McDonough CB Brindle PK Abel T Wood MA Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB:CBP-dependent transcriptional activation J Neurosci 27 6128 6140 2007 17553985 PMC2925045
[21]Chung YH Kim EJ Shin CM Joo KM Kim MJ Woo HW Cha CI Age-related changes in CREB binding protein immunoreactivity in the cerebral cortex and hippocampus of rats Brain Res 956 312 318 2002 12445700
[22]Trompet S Craen AJ Jukema JW Pons D Slagboom PE Kremer D Bollen EL Westendorp RG Variation in the CBP gene involved in epigenetic control associates with cognitive function Neurobiol Aging 32 549.e541 549.e548 2011 20096957
[24]Vermaak D Wade PA Jones PL Shi YB Wolffe AP Functional analysis of the SIN3-histone deacetylase RPD3-RbAp48-histone H4 connection in the Xenopus oocyte Mol Cell Biol 19 5847 5860 1999 10454532 PMC84434
[25]Mayford M Bach ME Huang YY Wang L Hawkins RD Kandel ER Control of memory formation through regulated expression of a CaMKII transgene Science 274 1678 1683 1996 8939850
[26]Resnick SM Trotman KM Kawas C Zonderman AB Age-associated changes in specific errors on the Benton Visual Retention Test J Gerontol B Psychol Sci Soc Sci 50 171 178 1995 7767695
[27]Schacter DL Cooper LA Valdiserri M Implicit and explicit memory for novel visual objects in older and younger adults Psychol Aging 7 299 308 1992 1610519
[28]Grady CL McIntosh AR Horwitz B Maisog JM Ungerleider LG Mentis MJ Pietrini P Schapiro MB Haxby JV Age-related reductions in human recognition memory due to impaired encoding Science 269 218 221 1995 7618082
[29]Moss MB Rosene DL Peters A Effects of aging on visual recognition memory in the rhesus monkey Neurobiol Aging 9 495 502 1988 3062461
[30]Rapp PR Amaral DG Evidence for task-dependent memory dysfunction in the aged monkey J Neurosci 9 3568 3576 1989 2795141 PMC6569903
[31]Erickson CA Barnes CA The neurobiology of memory changes in normal aging Exp Gerontol 38 61 69 2003 12543262
[32]Pavlopoulos E Trifilieff P Chevaleyre V Fioriti L Zairis S Pagano A Malleret G Kandel ER Neuralized1 activates CPEB3: A function for nonproteolytic ubiquitin in synaptic plasticity and memory storage Cell 147 1369 1383 2011 22153079 PMC3442370
[34]Pacifico F Paolillo M Chiappetta G Crescenzi E Arena S Scaloni A Monaco M Vascotto C Tell G Formisano S Leonardi A RbAp48 is a target of nuclear factor-κB activity in thyroid cancer J Clin Endocrinol Metab 92 1458 1466 2007 17244783
[35]Kong L Yu XP Bai XH Zhang WF Zhang Y Zhao WM Jia JH Tang W Zhou YB Liu CJ RbAp48 is a critical mediator controlling the transforming activity of human papillomavirus type 16 in cervical cancer J Biol Chem 282 26381 26391 2007 17616526
[36]Morris RG Garrud P Rawlins JN O’Keefe J Place navigation impaired in rats with hippocampal lesions Nature 297 681 683 1982 7088155
[37]Keith JR Wu Y Epp JR Sutherland RJ Fluoxetine and the dentate gyrus: Memory, recovery of function, and electrophysiology Behav Pharmacol 18 521 531 2007 17762521 PMC2668873
[38]Sumien N Sims MN Taylor HJ Forster MJ Profiling psychomotor and cognitive aging in four-way cross mice Age 28 265 282 2006 22253494 PMC3259154
[40]Lin W Celik A Paczynski RP Regional cerebral blood volume: A comparison of the dynamic imaging and the steady state methods J Magn Reson Imaging 9 44 52 1999 10030649
[41]Gaisler-Salomon I Miller GM Chuhma N Lee S Zhang H Ghoddoussi F Lewandowski N Fairhurst S Wang Y Conjard-Duplany A Masson J Balsam P Hen R Arancio O Galloway MP Moore HM Small SA Rayport S Glutaminase-deficient mice display hippocampal hypoactivity, insensitivity to pro-psychotic drugs and potentiated latent inhibition: Relevance to schizophrenia Neuropsychopharmacology 34 2305 2322 2009 19516252 PMC2811085
[42]Wu W Small SA Imaging the earliest stages of Alzheimer’s disease Curr Alzheimer Res 3 529 539 2006 17168652
[44]Valor LM Pulopulos MM Jimenez-Minchan M Olivares R Lutz B Barco A Ablation of CBP in forebrain principal neurons causes modest memory and transcriptional defects and a dramatic reduction of histone acetylation but does not affect cell viability J Neurosci 31 1652 1663 2011 21289174 PMC6623752
[45]Cvekl A Duncan MK Genetic and epigenetic mechanisms of gene regulation during lens development Prog Retin Eye Res 26 555 597 2007 17905638 PMC2136409
[46]Sahay A Scobie KN Hill AS O’Carroll CM Kheirbek MA Burghardt NS Fenton AA Dranovsky A Hen R Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation Nature 4 72 466 470 2011 PMC3084370 21460835
[47]Berchtold NC Cribbs DH Coleman PD Rogers J Head E Kim R Beach T Miller C Troncoso J Trojanowski JQ Zielke HR Cotman CW Gene expression changes in the course of normal brain aging are sexually dimorphic Proc Natl Acad Sci USA 105 15605 15610 2008 18832152 PMC2563070
[48]Bach ME Barad M Son H Zhuo M Lu YF Shih R Mansuy I Hawkins RD Kandel ER Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway Proc Natl Acad Sci USA 96 5280 5285 1999 10220457 PMC21855
[49]Silva AJ Simpson EM Takahashi JS Lipp HP Nakanishi S Wehner JM Giese KP Tully T Abel T Chapman PF Fox K Grant S Itohara S Lathe R Mayford M McNamara JO Morris RJ Picciotto M Roder J Shin HS Slesinger PA Storm DR Stryker MP Tonegawa S Wang Y Wolfer DP Mutant mice and neuroscience: Recommendations concerning genetic background. Banbury Conference on Genetic Background in Mice Neuron 19 755 759 1997 9354323
[50]Hawrylycz MJ Lein ES Guillozet-Bongaarts AL Shen EH Ng L Miller JA van de Lagemaat LN Smith KA Ebbert A Riley ZL Abajian C Beckmann CF Bernard A Bertagnolli D Boe AF Cartagena PM Chakravarty MM Chapin M Chong J Dalley RA Daly BD Dang C Datta S Dee N Dolbeare TA Faber V Feng D Fowler DR Goldy J Gregor BW Haradon Z Haynor DR Hohmann JG Horvath S Howard RE Jeromin A Jochim JM Kinnunen M Lau C Lazarz ET Lee C Lemon TA Li L Li Y Morris JA Overly CC Parker PD Parry SE Reding M Royall JJ Schulkin J Sequeira PA Slaughterbeck CR Smith SC Sodt AJ Sunkin SM Swanson BE Vawter MP Williams D Wohnoutka P Zielke HR Geschwind DH Hof PR Smith SM Koch C Grant SG Jones AR An anatomically comprehensive atlas of the adult human brain transcriptome Nature 489 391 399 2012 22996553 PMC4243026

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Methylation polymorphism influences practice effects in children during attention tasks
Voelker, P., Sheese, B. E., Rothbart, M. K., & Posner, M. I. (2016) · Cognitive Neuroscience · doi:10.1080/17588928.2016.1170006 · Cited by 53 · see citing works
“There are several forms of epigenetic change, and among the most studied involve changes related to histones in memory formation (Pavlopoulos et al., 2013; Peleg et al., 2010) and to DNA methylation (Day et al., 2013; McGowan et al., 2009).”
Background
Brain regions vulnerable and resistant to aging without Alzheimer’s disease
Feng, X., Guo, J., Sigmon, H. C., Sloan, R. P., Brickman, A. M., Provenzano, F. A., Small, S. A., & Initiative, A. D. N. (2020) · PLoS ONE · doi:10.1371/journal.pone.0234255 · Cited by 48 · see citing works
“This finding was validated in mouse models, showing that RbAp48 plays causal role in agerelated memory decline [16].”
BackgroundMethodResultSelf-citation
Aging- and injury-related differential apoptotic response in the dentate gyrus of the hippocampus in rats following brain trauma
Sun, D., McGinn, M. J., Hankins, J. E., Mays, K., Rolfe, A., & Colello, R. (2013) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2013.00095 · Cited by 41 · see citing works
Retinoblastoma-binding Protein 4-regulated Classical Nuclear Transport Is Involved in Cellular Senescence*
Tsujii, A., Miyamoto, Y., Moriyama, T., Tsuchiya, Y., Obuse, C., Mizuguchi, K., Oka, M., & Yoneda, Y. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.681908 · Cited by 40 · see citing works
“Knockdown of RBBP4 Induces Cellular Senescence by Impairing the Nuclear Transport—RBBP4 was originally identified as an aging-associated molecule (11, 12).”
Background
Memory Decline and Its Reversal in Aging and Neurodegeneration Involve miR-183/96/182 Biogenesis
Jawaid, A., Woldemichael, B. T., Kremer, E. A., Laferrière, F., Gaur, N., Afroz, T., Polymenidou, M., & Mansuy, I. M. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1314-3 · Cited by 47 · see citing works
Recent Advances in Mouse Models of Sjögren's Syndrome
Gao, Y., Chen, Y., Zhang, Z.-J., Yu, X.-H., & Zheng, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01158 · Cited by 37 · see citing works
The Endocrine Function of Osteocalcin Regulated by Bone Resorption: A Lesson from Reduced and Increased Bone Mass Diseases
Rossi, M., Battafarano, G., Pepe, J., Minisola, S., & Fattore, A. D. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20184502 · Cited by 44 · see citing works
“Interestingly, reduction of RbAp48 expression is a molecular hallmark of memory loss correlated with aging in humans and mice [53].”
Background
Reversal of Age-Related Learning Deficiency by the Vertebrate PACAP and IGF-1 in a Novel Invertebrate Model of Aging: The Pond Snail (Lymnaea stagnalis)
Pirger, Z., Naskar, S., László, Z., Kemenes, G., Reglodi, D., & Kemenes, I. (2014) · The journals of gerontology. Series A, Biological sciences and medical sciences · doi:10.1093/gerona/glu068 · Cited by 37 · see citing works
“RbAp48 is known to interact with a complex of CREB binding protein (CBP, a histone acetyl transferase) and phosphorylated CREB1 (pCREB1) (6) and thus it was hypothesized that enhancement of the PKA-CREB1-CBP pathway and the RbAp48 protein could be a target for therapeutic interventions targeting age-related memory los…”
Background
Increased GSNOR Expression during Aging Impairs Cognitive Function and Decreases S-Nitrosation of CaMKIIα
Zhang, Y., Wu, K., Su, W., Zhang, D., Wang, P., Qiao, X., Yao, Q., Yuan, Z., Yao, Y., Liu, G., et al. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.0681-17.2017 · Cited by 43 · see citing works
“GSNOR is a new potential target of age-related cognitive impairment Scientists are searching for key driver molecules in this process as specific targets to decrease age-related cognitive impairment (Peleg et al., 2010; Ménard et al., 2013; Pavlopoulos et al., 2013; Johnson et al., 2015; Sharma et al., 2015; Smith et…”
Background
Sericin modulates learning and memory behaviors by tuning of antioxidant, inflammatory, and apoptotic markers in the hippocampus of aged mice
Seyedaghamiri, F., Farajdokht, F., Vatandoust, S. M., Mahmoudi, J., Khabbaz, A., & Sadigh‐Eteghad, S. (2021) · Molecular Biology Reports · doi:10.1007/s11033-021-06195-2 · Cited by 38 · see citing works
Alzheimer's Disease and Histone Code Alterations.
Narayan, P., & Dragunow, M. (2017) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-53889-1_17 · Cited by 33 · see citing works
“performance which correlated with loss of CBP mediated histone acetylation, which was rescued when RbAp48 was reintroduced in the dentate gyrus via viral vector(61).”
Background
Three midlife strategies to prevent cognitive impairment due to Alzheimer's disease
Henderson, V. W. (2014) · Climacteric · doi:10.3109/13697137.2014.929650 · Cited by 31 · see citing works
Loss of RBBP4 results in defective inner cell mass, severe apoptosis, hyperacetylated histones and preimplantation lethality in mice†
Miao, X., Sun, T., Barletta, H. L., Mager, J., & Cui, W. (2020) · Biology of Reproduction · doi:10.1093/biolre/ioaa046 · Cited by 37 · see citing works
“Interestingly, RBBP4 has also been implicated in other biological processes, such as cell proliferation and apoptosis [27], nuclear transport and cellular senescence [28], DNA repair and tumorigenesis [29], as well as age-related memory loss [30].”
Background
TORC2: a novel target for treating age-associated memory impairment
Johnson, J. L., Huang, W., Roman, G., & Costa‐Mattioli, M. (2015) · Scientific Reports · doi:10.1038/srep15193 · Cited by 32 · see citing works
Intravenous ascorbate improves spatial memory in middle-aged APP/PSEN1 and wild type mice
Kennard, J. A., & Harrison, F. E. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.01.044 · Cited by 26 · see citing works
Osteocalcin, ovarian senescence, and brain health
Schatz, M., Saravanan, S., d’Adesky, N., Bramlett, H. M., Pérez‐Pinzón, M. A., & Raval, A. P. (2020) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2020.100861 · Cited by 30 · see citing works
Chronic Polyphenon-60 or Catechin Treatments Increase Brain Monoamines Syntheses and Hippocampal SIRT1 LEVELS Improving Cognition in Aged Rats
Ramis, M. R., Sarubbo, F., Tejada, S., Jiménez-García, M., Esteban, S., Miralles, A., & Moranta, D. (2020) · Nutrients · doi:10.3390/nu12020326 · Cited by 30 · see citing works
“Finally, another protein that modulates histone acetylation patterns, the histone-binding protein RBAP46/48, has also been associated with age-related memory loss [34,35]; its role in the neuroprotective effects of polyphenolic compounds has not been investigated.”
Background
Preclinical Magnetic Resonance Imaging and Spectroscopy Studies of Memory, Aging, and Cognitive Decline
Febo, M., & Foster, T. C. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00158 · Cited by 27 · see citing works
“…relationship between transcriptional markers of aging or neurodegenerative disease and the progression brain changes (Song et al., 2004; Maheswaran et al., 2009; Moreno et al., 2012; Lewandowski et al., 2013; Pavlopoulos et al., 2013; Zerbi et al., 2014; Micotti et al., 2015; Sevgi et al., 2015).”
Background
Genetic variants in a ‘cAMP element binding protein’ (CREB)-dependent histone acetylation pathway influence memory performance in cognitively healthy elderly individuals
Barral, S., Reitz, C., Small, S. A., & Mayeux, R. P. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.06.024 · Cited by 28 · see citing works
“Recently, gene expression analysis of human postmortem tissue harvested from the hippocampal formation identified a substantial age-related decline in the expression of the histone-binding protein RbAp48 gene (Pavlopoulos et al., 2013).”
Self-citation
ATP-dependent chromatin remodelers in ageing and age-related disorders
Swer, P. B., & Sharma, R. (2021) · Biogerontology · doi:10.1007/s10522-020-09899-3 · Cited by 25 · see citing works
Synaptic Pruning in Alzheimer’s Disease: Role of the Complement System
Brucato, F. H., & Benjamin, D. E. (2020) · Global Journal of Medical Research · doi:10.34257/gjmrfvol20is6pg1 · Cited by 22 · see citing works
Decrease of delta oscillatory responses is associated with increased age in healthy elderly.
Emek-Savaş, D. D., Güntekin, B., Yener, G., & Basar, E. (2014) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2015.02.006 · Cited by 24 · see citing works
The reverse control of irreversible biological processes
Cho, K., Joo, J. I., Shin, D., Kim, D., & Park, S. (2016) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1346 · Cited by 20 · see citing works
“By injecting RbAp48 in an old mouse, the differential histone acetylation and activity of protein kinase A (PKA)/cAMP responsive element binding protein 1 (CREB1) pathway, central molecular signaling molecules of memory and synaptic plasticity phenotype, are observed at the cellular level.(53) Moreover, this pathway a…”
Background
DLX1 and the NuRD complex cooperate in enhancer decommissioning and transcriptional repression
Price, J. D., Lindtner, S., Ypsilanti, A. R., Binyameen, F., Johnson, J. R., Newton, B. W., Krogan, N. J., & Rubenstein, J. L. R. (2022) · Development · doi:10.1242/dev.199508 · Cited by 25 · see citing works
Mitochondrial aconitase 1 regulates age‐related memory impairment via autophagy/mitophagy‐mediated neural plasticity in middle‐aged flies
Cho, Y., Kim, G., & Park, J. (2021) · Aging Cell · doi:10.1111/acel.13520 · Cited by 18 · see citing works
“Molecular mechanism for agerelated memory loss: The histone- binding protein RbAp48.”
BackgroundInfluential
Effect of Transcranial Near-Infrared Light 1068 nm Upon Memory Performance in Aging Healthy Individuals: A Pilot Study
Dougal, G., Ennaceur, A., & Chazot, P. (2021) · Photobiomodulation, photomedicine, and laser surgery · doi:10.1089/photob.2020.4956 · Cited by 19 · see citing works
Potential fluid biomarkers for pathological brain changes in Alzheimer's disease: Implication for the screening of cognitive frailty
Ruan, Q., D’Onofrio, G., Sancarlo, D., Greco, A., & Yu, Z. (2016) · Molecular Medicine Reports · doi:10.3892/mmr.2016.5618 · Cited by 17 · see citing works
“Similar memory deficits were also observed in RbAp48‑deficient transgenic mice (37).”
Epigenetic mechanisms in Alzheimer's disease
Balázs, R. (2014) · Degenerative Neurological and Neuromuscular Disease · doi:10.2147/dnnd.s37341 · Cited by 13 · see citing works
“17 genes showing reliable age-related changes.(43) The most significant change was an age-related decline in retinoblastoma-binding protein p48 (RbAp48), a histone-binding protein that is present in protein complexes involved in histone acetylation and chromatin assembly.”
Lead exposure induces neuronal apoptosis via NFκB p65/RBBP4/Survivin signaling pathway.
Chen, H., Zhang, W., Luo, S., Li, Y.-S., Zhu, Q., Xia, Y.-L., Tan, H., Bian, Y., Li, Y.-B., Ma, J.-M., et al. (2023) · Toxicology · doi:10.1016/j.tox.2023.153654 · Cited by 18
The proteomic investigation reveals interaction of mdig protein with the machinery of DNA double-strand break repair
Wang, W., Lu, Y.-J., Stemmer, P., Zhang, X.-M., Bi, Y.-Y., Yi, Z., & Chen, F. (2015) · OncoTarget · doi:10.18632/oncotarget.4961 · Cited by 18 · see citing works
“Furthermore, it is especially interesting to note that RBBP4 has been linked to the human aging process with hippocampus-related memory loss [37].”
Background
The conserved histone chaperone LIN‐53 is required for normal lifespan and maintenance of muscle integrity in Caenorhabditis elegans
Müthel, S., Uyar, B., He, M., Krause, A., Vitrinel, B., Bulut, S., Vasiljević, D., Marchal, I., Kempa, S., Akalin, A., et al. (2019) · Aging Cell · doi:10.1111/acel.13012 · Cited by 24 · see citing works
“Interestingly, it has recently been revealed that the decline of RBBP4 in humans causes cognitive aging and memory loss (Pavlopoulos et al., 2013).”
Background
TSPYL2 Regulates the Expression of EZH2 Target Genes in Neurons
Liu, H., Peng, L., So, J., Tsang, K.-H., Chong, C. H., Mak, P., Chan, K.-M., & Chan, S. Y. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1238-y · Cited by 17 · see citing works
A Temporal Activity of CA1 Neurons Underlying Short-Term Memory for Social Recognition Altered in PTEN Mouse Models of Autism Spectrum Disorder
Chai, A., Chen, X.-F., Xu, X.-S., Zhang, N., Li, M., Li, J., Zhang, L., Zhang, D., Zhang, X., Mao, R., et al. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.699315 · Cited by 23 · see citing works
Lead Discovery for Alzheimer's Disease Related Target Protein RbAp48 from Traditional Chinese Medicine
Huang, H.-J., Lee, C.-C., & Chen, C. Y.-C. (2014) · BioMed Research International · doi:10.1155/2014/764946 · Cited by 15 · see citing works
“have demonstrated that Retinoblastoma-associated protein (RbAp48) deficiency or loss of function in the dentate gyrus (DG) is related to agerelated memory loss [9].”
Background
Interpreting the molecular mechanisms of RBBP4/7 and their roles in human diseases (Review)
Zhan, Y., Yin, A., Su, X., Tang, N., Zhang, Z., Chen, Y. G., Wang, W., & Wang, J. (2024) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2024.5372 · Cited by 15 · see citing works
“Its expression in human and mouse brains declines with age, affecting memory forma‑ tion (81).”
Background
Altered Gene Expression in Prefrontal Cortex of a Fabry Disease Mouse Model
Kummer, K. K., Kalpachidou, T., Mitrić, M. M., Langeslag, M., & Kress, M. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00201 · Cited by 17 · see citing works
“The histone-binding protein Rbbp4, which was downregulated in our screen, is involved in age-related memory loss, and inhibition of this gene causes hippocampus dependent memory deficits in young mice (Pavlopoulos et al., 2013).”
Background
The Role of Aging in Alzheimer’s Disease
Kerchner, G. A., & Wyss‐Coray, T. (2015) · Springer eBooks · doi:10.1007/978-3-319-23246-1_7 · Cited by 14 · see citing works
Effect of zileuton on osteoporotic bone and its healing, expression of bone, and brain genes in rats
Saul, D., Ninković, M., Komrakova, M., Wolff, L., Simka, P., Gasimov, T., Menger, B., Hoffmann, D. B., Rohde, V., & Sehmisch, S. (2017) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01126.2016 · Cited by 15 · see citing works
“functions partially trough CREB pathway (57).”
Background
Compromised Object Pattern Separation Performance in Parkinson′s Disease Suggests Dentate Gyrus Neurogenesis may be Compromised in the Condition
Wesnes, K. A. (2014) · Journal of Alzheimer’s Disease & Parkinsonism · doi:10.4172/2161-0460.1000131 · Cited by 8 · see citing works
“Evidence has just appeared firmly linking RbAp48 (a histone-binding protein that modifies histone acetylation) with dentate gyrus neurogenesis and age-related memory loss [6].”
Background
Deep learning of MRI contrast enhancement for mapping cerebral blood volume from single-modal non-contrast scans of aging and Alzheimer's disease brains
Liu, C., Zhu, N., Sun, H., Zhang, J., Feng, X., Gjerswold-Selleck, S. J., Sikka, D., Zhu, X., Liu, X., Nuriel, T., et al. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.923673 · Cited by 11 · see citing works
“Through our previous study in mapping functional brain lesions that localize to specific regions of the hippocampal formation, we have extensively used GBCAs to generate quantitative, high-resolution CBV maps (Small et al., 2011; Pavlopoulos et al., 2013; Schobel et al., 2013; Brickman et al., 2014; Khan et al., 2014;…”
MethodResultSelf-citation
Chromatin Remodeling in the Brain-a NuRDevelopmental Odyssey
Larrigan, S., Shah, S., Fernandes, A., & Mattar, P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094768 · Cited by 11 · see citing works
Pharmacological chaperones in the age of proteomic pathology
Small, S. (2014) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1413111111 · Cited by 11
Self-citation
Neurochemical and Cognitive Beneficial Effects of Moderate Physical Activity and Catechin in Aged Rats
Ramis, M., Sarubbo, F., Moranta, D., Tejada, S., Lladó, J., Miralles, A., & Esteban, S. (2021) · Antioxidants · doi:10.3390/antiox10040621 · Cited by 10 · see citing works
“Another protein expressed in the hippocampus associated with age-related memory loss is RbAp (histone-binding protein RbAp48/retinoblastoma-binding protein), which also modulates histone acetylation patterns similar to SIRT1 [18,19].”
Background
Hippocampal Damage During Mechanical Ventilation in Trendelenburg Position: A Secondary Analysis of an Experimental Study on the Prevention of Ventilator-Associated Pneumonia.
López-Aguilar, J., Bassi, G. L., Quílez, M. E., Martí, J., Ranzani, O., Xiol, E. A., Rigol, M., Luque, N., Guillamat, R., Ferrer, I., et al. (2019) · Shock · doi:10.1097/shk.0000000000001237 · Cited by 10 · see citing works
“Interestingly, in our latest animal study, we specifically found changes in the dentate gyrus, which plays a pivotal role in learning and memory (34).”
Background
Tactile learning in rodents: Neurobiology and neuropharmacology.
Roohbakhsh, A., Shamsizadeh, A., Arababadi, M., Ayoobi, F., Fatemi, I., Allahtavakoli, M., & Mohammad-Zadeh, M. (2016) · Life Science · doi:10.1016/j.lfs.2016.01.031 · Cited by 9 · see citing works
Network Biology Approaches to Uncover Therapeutic Targets Associated with Molecular Signaling Pathways from circRNA in Postoperative Cognitive Dysfunction Pathogenesis
Bhuiyan, P., Chuwdhury, G., Sun, Z., Chen, Y., Dong, H., Ahmed, F. F., Li, N., Rahman, M. H., & Qian, Y. (2022) · Journal of Molecular Neuroscience · doi:10.1007/s12031-022-02042-6 · Cited by 10 · see citing works
“The study found that RBAP4 interacts with histone and modifies histone acetylation, thus regulating memory consolidation and cognitive function (Pavlopoulos et al. 2013).”
Background
Rodent Mazes and Memory: Continuing the Search for the Engram
Bimonte‐Nelson, H. A. (2014) · Neuromethods · doi:10.1007/978-1-4939-2159-1_1 · Cited by 6 · see citing works
Elevated neuroglobin lessens neuroinflammation and alleviates neurobehavioral deficits induced by acute inhalation of combustion smoke in the mouse
Gorgun, M. F., Zhuo, M., Dineley, K., & Englander, E. (2019) · Neurochemical Research · doi:10.1007/s11064-019-02856-8 · Cited by 6 · see citing works
Clinical Genetics and Genomics of Aging
Gómez-Verjan, J. C., & Rivero-Segura, N. A. (2020) · doi:10.1007/978-3-030-40955-5 · Cited by 5
Mechanisms of electromagnetic influences and effects on membrane systems in neurons and cardiomyocytes
Orlov, V. I., Rudenko, M., Shikhlyarova, A., Sukhov, A. A., Kirichenko, E., Filippova, S., Zernov, V., Makedonsky, D., Mamberger, K., & Rudenko, S. (2017) · doi:10.12710/cardiometry.2017.11.1727 · Cited by 4
Flavanol-rich food for thought
Pa, J., & Gazzaley, A. (2014) · Nature Neuroscience · doi:10.1038/nn.3876 · Cited by 4 · see citing works
Deep Learning Substitutes Gadolinium in Detecting Functional and Structural Brain Lesions with MRIPreprint
Liu, C., Zhu, N., Sikka, D., Feng, X., Sun, H., Liu, X., Gjerswold-Selleck, S. J., Wei, H.-J., Upadhyayula, P. S., Mela, A., et al. (2020) · Research Square · doi:10.21203/rs.3.rs-56518/v1 · Cited by 4 · see citing works
Self-citation
Trichloroethylene: Toxicity and Health Risks
Gilbert, K., & Blossom, S. (2014) · Molecular and Integrative Toxicology · doi:10.1007/978-1-4471-6311-4 · Cited by 4
Epigenetic Alterations due to Trichloroethylene
Cooney, C. A. (2014) · Molecular and integrative toxicology · doi:10.1007/978-1-4471-6311-4_10 · Cited by 1 · see citing works
“Recently, RbAp48, a natural histone deacetylase inhibitor protein, has been shown to help regulate both histone acetylation and memory (Pavlopoulos et al. 2013 ).”
Background
The dual role of ATF4 in neurons: from stress adaptation to therapeutic intervention
Huang, H., Xu, Y., Li, X.-Y., Li, C.-G., & Peng, W. (2026) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2026.1816333 · Cited by 2 · see citing works
“…as activity-regulated cytoskeleton-associated protein (Arc) and brain-derived neurotrophic factor (BDNF; Bartsch et al., 1995; Chen et al., 2003; Pavlopoulos et al., 2013), while simultaneously engaging epigenetic modulators like JMJD3 to prime pro-regenerative programs (Weng et al., 2018;…”
Inhibition of histone lysine demethylase restores learning and memory in aged micePreprint
Bhatt, S. R., MacBean, L. F., Kramár, E. A., Pérez‐Sisqués, L., Smethurst, P., Robb, J. L., Jindal, N., Fetterly, T. L., Graham, A., Wood, M. A., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.22.695858
“Aged mice exhibit deficits in spatial [3-6], associative [7-8], and hippocampus-independent memory [9-10].”
Age-Dependent Changes in Taurine, Serine, and Methionine Release in the Frontal Cortex of Awake Freely-Moving Rats: A Microdialysis Study
Cueto-Ureña, C., Ramírez-Expósito, M., Carrera-González, M., & Martínez-Martos, J. (2025) · Life · doi:10.3390/life15020295 · Cited by 2 · see citing works
“Furthermore, exploring the underlying mechanisms behind the reduced evoked release could provide deeper insights into the neurochemical changes associated with aging.”
Anatomical biology guides a search for nutrients for the aging brain
Lauriola, V., Brickman, A., Sloan, R., & Small, S. (2022) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2022.101154 · Cited by 2 · see citing works
Self-citation
Rapidly evolving in humans topologically associating domainsPreprint
Glinsky, G. V. (2015) · arXiv (Cornell University) · doi:10.48550/arxiv.1507.05368 · Cited by 1 · see citing works
“Furthermore, significant age-associated decline of expression in dentate gyrus subregion of the hippocampus of one of the NuRD complex subunits, RbAp48 (RBBP4), was mechanistically connected with the age-related memory loss in humans (Pavlopoulos et al., 2013).”
Background
Human-specific genomic features of pluripotency regulatory networks link NANOG with fetal and adult brain developmentPreprint
Glinsky, G. V. (2015) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/022913 · Cited by 30 · see citing works
“Furthermore, significant age-associated decline of expression in dentate gyrus sub-region of the hippocampus of one of the NuRD complex subunits, RbAp48 (RBBP4), was mechanistically connected with the age-related memory loss in humans (Pavlopoulos et al., 2013).”
Background
Chronic stress contributes to long-term isoflurane anesthesia-induced cognitive dysfunction via histone acetylation modulated by RbAp48-HDAC2 in male mice
Shao, Y., Zheng, Z., Chen, C., Zhou, J., Fang, X., Gong, X., & Xia, T. (2025) · Journal of Anesthesia and Translational Medicine · doi:10.1016/j.jatmed.2025.04.003 · Cited by 1 · see citing works
“21 However, the specific role of RbAp48 in PND pathogenesis remains elusive.”
Loss of Immunohistochemical Reactivity in Association With Handling-induced Dark Neurons in Mouse Brains
Soontornniyomkij, V., Chang, R. C., Soontornniyomkij, B., Schilling, J., Patel, H. H., & Jeste, D. (2020) · Toxicologic pathology (Print) · doi:10.1177/0192623319896263 · Cited by 1
Is Alzheimer's Disease an Irreversible Loss of Memory Function with No Hope of Return?
Kraus, J. (2014) · doi:10.4236/psych.2014.55047 · Cited by 1
“Nevertheless, recent studies seem to agree that memories are made presumably in the constitutive matter of two specific brain regions: cerebral cortex (Hasan et al., 2013) or/and “hippocampus” (Pavlopoulos et al., 2013).”
Background
Memory: RBAP48 drives age-related memory loss
Flight, M. H. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3603 · Cited by 1
Epigenetics and Ageing
Monroy‐Jaramillo, N., & Vázquez-Martínez, E. R. (2020) · Springer eBooks · doi:10.1007/978-3-030-40955-5_8 · Cited by 3 · see citing works
Effect of Chronic Dark Chocolate or Cocoa Intake on Cognitive Function: A Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-Assessed Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Arabpour, Z., Arabpour, Z., & Jazayeri, S. (2026) · Nutrition reviews · doi:10.1093/nutrit/nuaf286
Epigenetic Mechanisms in Perioperative Medicine: From Neuroinflammation and NETosis to Organ Dysfunction and Precision Therapeutics
Rump, K., & Adamzik, M. (2026) · Biomedicines · doi:10.3390/biomedicines14081658
“One important contributor might be histone-binding protein RBBP4 (also known as RbAp48) [55], which is suspected to be the main cause of memory loss in normal aging.”
Biology of cognitive aging across species
Kakizawa, S., Park, J., & Tonoki, A. (2023) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/ggi.14782
“113 Several factors associated with AMI have been identi ﬁ ed in fruit ﬂ ies.”
Background

Authors: Pavlopoulos, E., Jones, S., Kosmidis, S., Close, M., Kim, C., Kovalerchik, O., Small, S. A., & Kandel, E. R.
Affiliations: Howard Hughes Medical Institute (US)
Columbia University (US)
Corresponding author: Jones, Sidonie
Kosmidis, Stylianos
Small, Scott A.
Kandel, Eric R.
ORCID: Kosmidis, Stylianos
Kim, Carla
Small, Scott A.
Kandel, Eric R.
Venue: Science Translational Medicine
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2013-08-28
Volume: 5
Issue: 200
Pages: 200ra115-200ra115
ISSN: 1946-6234 (ISSN-L)
1946-6242
DOI: 10.1126/scitranslmed.3006373
PMC: PMC4940031
OpenAlex: W2104064321
Cited by: 109
References: 50
Citations by year: 2026: 3 · 2025: 3 · 2024: 1 · 2023: 5 · 2022: 6 · 2021: 7 · 2020: 12 · 2019: 7 · 2018: 6 · 2017: 10 · 2016: 10 · 2015: 12 · 2014: 22 · 2013: 5
FWCI: 8.96
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Science Translational Medicine (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Aging (R01AG034618, R01AG025161, P50AG008702)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords: age-related memory decline, RbAp48, histone-binding proteins, histone acetylation, dentate gyrus, hippocampus, cognitive aging, Alzheimer's disease, gene expression profiling, hippocampal-dependent memory, entorhinal cortex, novel object recognition, Morris water maze
MeSH terms: Acetylation, Adult, Aged, Aged, 80 and over, Aging, Animals, Female, Genes, Dominant, Histones, Humans, Male, Membrane Proteins, Memory Disorders, Middle Aged, Organ Specificity, Phosphoproteins, Protein Binding, RNA, Messenger, Gene Expression Regulation, Developmental, Dentate Gyrus, Oligonucleotide Array Sequence Analysis, Mice, Histone Acetyltransferases, Retinoblastoma-Binding Protein 4

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Molecular Mechanism for Age-Related Memory Loss: The Histone-Binding Protein RbAp48

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