Novel Combinatorial Therapeutic Targeting of PAI-1(SERPINE1) Gene Expression in Alzheimer’s Disease

M. Kutz, Stacie; E. Higgins, Craig; J. Higgins, Paul

doi:10.4172/2324-8769.1000106

Cited by 36Alzheimer's disease research and treatmentsProtease and Inhibitor MechanismsNeuroinflammation and Neurodegeneration Mechanisms

Novel Combinatorial Therapeutic Targeting of PAI-1(SERPINE1) Gene Expression in Alzheimer’s Disease

Open access

M. Kutz, Stacie, E. Higgins, Craig, J. Higgins, Paul·2012·Molecular Medicine & Therapeutics

DOI 10.4172/2324-8769.1000106PMC PMC3703665

Open this paper in CoChat — free account

Abstract

Accumulation of neurotoxic amyloid peptides (Aβ) in the brain, generated by β-site proteolytic processing of the amyloid precursor protein (APP), is the hallmark pathophysiologic feature of Alzheimer's disease. The plasmin-activating cascade, in which urokinase (uPA) and tissue-type (tPA) plasminogen activators convert plasminogen to the broad-spectrum protease plasmin, appears to serve a protective, Aβ-clearing, role in the central nervous system. Plasmin degrades Aβ and catalyzes α- site APP proteolysis generating nontoxic peptides. Plasmin activation in the brain is negatively regulated by the fast-acting clade E serine protease inhibitor (SERPIN) plasminogen activator inhibitor type-1 (PAI-1; SERPINE1) resulting in Aβ accumulation. PAI-1 and its major physiological inducer TGF-β1, moreover, are both increased in Alzheimer's disease models and implicated in the etiology and progression of human neurodegenerative disorders. Current findings support the hypothesis that targeting of PAI-1 function (by small molecule drugs) and/or gene expression (by histone deacetylase inhibitors) may constitute a clinically-relevant molecular approach to the therapy of neurodegenerative diseases associated with increased PAI-1 levels.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.4172/2324-8769.1000106

Cites

28 of 28 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

SerpinE1 was downregulated in Plexin-B1-deficient astrocytes.
“Of interest in the context of AD was also the downregulation of SerpinE1 (plasminogen activator inhibitor), whose inhibition has been proposed as a therapeutic strategy to reduce amyloid load49.”
From Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease (2024) · cites this paper as [49]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., & Cole, G. (1996) · Science · doi:10.1126/science.274.5284.99 · Cited by 4,210 · see citing works
β-Secretase Cleavage of Alzheimer's Amyloid Precursor Protein by the Transmembrane Aspartic Protease BACE
Vassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Denis, P., Teplow, D. B., Ross, S., Amarante, P., Loeloff, R., et al. (1999) · Science · doi:10.1126/science.286.5440.735 · Cited by 3,876 · see citing works
Alzheimer's disease and Down's syndrome: Sharing of a unique cerebrovascular amyloid fibril protein
Glenner, G. G., & Wong, C. W. (1984) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(84)91209-9 · Cited by 1,693 · see citing works
Translating cell biology into therapeutic advances in Alzheimer's disease
Selkoe, D. J. (1999) · Nature · doi:10.1038/399a023 · Cited by 1,588 · see citing works
The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases
MCGEER, P., & MCGEER, E. (1995) · Brain Research Reviews · doi:10.1016/0165-0173(95)00011-9 · Cited by 1,287 · see citing works
The Serpins Are an Expanding Superfamily of Structurally Similar but Functionally Diverse Proteins
Silverman, G. A., Bird, P. I., Carrell, R. W., Church, F., Coughlin, P., Gettins, P. G. W., Irving, J. A., Lomas, D. A., Luke, C. J., Moyer, R. W., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.r100016200 · Cited by 1,230 · see citing works
Recovery of learning and memory is associated with chromatin remodelling
Fischer, A., Sananbenesi, F., Wang, X., Dobbin, M., & Tsai, L.-H. (2007) · Nature · doi:10.1038/nature05772 · Cited by 1,227 · see citing works
Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and βAPP processing
Yu, G., Nishimura, M., Arawaka, S., Levitan, D. J., Zhang, L., Tandon, A., Song, Y., Rogaeva, E. A., Chen, F., Kawarai, T., et al. (2000) · Nature · doi:10.1038/35024009 · Cited by 906 · see citing works
The HDAC inhibitor, sodium butyrate, stimulates neurogenesis in the ischemic brain
Kim, H. J., Leeds, P., & Chuang, D. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06212.x · Cited by 332 · see citing works
The Plasmin System Is Induced by and Degrades Amyloid-β Aggregates
Tucker, H. M., Kihiko‐Ehmann, M., Caldwell, J. N., Wright, S., Kawarabayashi, T., PRICE, D. A., Walker, D., Scheff, S. W., McGillis, J. P., Rydel, R. E., et al. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-11-03937.2000 · Cited by 306 · see citing works
Multiple, diverse senile plaque–associated proteins are ligands of an apolipoprotein e receptor, the α2‐macroglobulin receptor/low‐density‐lipoprotein receptor—related protein
Rebeck, G. W., Harr, S. D., Hyman, B. T., & Strickland, D. K. (1995) · Annals of Neurology · doi:10.1002/ana.410370212 · Cited by 294 · see citing works
Chronic Overproduction of Transforming Growth Factor-β1 by Astrocytes Promotes Alzheimer's Disease-Like Microvascular Degeneration in Transgenic Mice
Wyss‐Coray, T., Lin, C., Sanan, D. A., Mucke, L., & Masliah, E. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64713-x · Cited by 224 · see citing works
Brain plasmin enhances APP α‐cleavage and Aβ degradation and is reduced in Alzheimer's disease brains
Ledesma, M. D., Silva, J. S. D., Craessaerts, K., Delacourte, A., Strooper, B. D., & Dotti, C. G. (2000) · EMBO Reports · doi:10.1093/embo-reports/kvd107 · Cited by 216 · see citing works
The Tissue Plasminogen Activator-Plasminogen Proteolytic Cascade Accelerates Amyloid-β (Aβ) Degradation and Inhibits Aβ-Induced Neurodegeneration
Melchor, J. P., Pawlak, R., & Strickland, S. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-26-08867.2003 · Cited by 202 · see citing works
Cleavage of Alzheimer's Amyloid Precursor Protein by α-Secretase Occurs at the Surface of Neuronal Cells
Parvathy, S., Hussain, I., Karran, E. H., Turner, A. J., & Hooper, N. M. (1999) · Biochemistry · doi:10.1021/bi9906827 · Cited by 200 · see citing works
Enhanced clearance of Aβ in brain by sustaining the plasmin proteolysis cascade
Jacobsen, J. S., Comery, T. A., Martone, R. L., Elokdah, H. M., Crandall, D. L., Oganesian, A., Aschmies, S., Kirksey, Y. M., Gonzales, C., Xu, J., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0710823105 · Cited by 146 · see citing works
Transforming Growth Factor-β1 Potentiates Amyloid-β Generation in Astrocytes and in Transgenic Mice
Lesné, S., Docagne, F., Gabriel, C., Liot, G., Lahiri, D. K., Buée, L., Plawinski, L., Delacourte, A., MacKenzie, E. T., Buisson, A., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300819200 · Cited by 142 · see citing works
Plasmin Cleavage of the Amyloid β-Protein: Alteration of Secondary Structure and Stimulation of Tissue Plasminogen Activator Activity
Nostrand, W. E. V., & Porter, M. D. (1999) · Biochemistry · doi:10.1021/bi990610f · Cited by 113 · see citing works
Serine Protease Inhibitors: Novel Therapeutic Targets for Stroke?
Vivien, D., & Buisson, A. (2000) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200005000-00001 · Cited by 99 · see citing works
Knockout of plasminogen activator inhibitor 1 gene reduces amyloid beta peptide burden in a mouse model of Alzheimer's disease
Liu, R., Groen, T. V., Katre, A. K., Cao, D., Kadisha, I., Ballinger, C. A., Wang, L., Carroll, S. L., & Li, L. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.06.003 · Cited by 95 · see citing works
Attenuation of vascular dementia by sodium butyrate in streptozotocin diabetic rats
Sharma, B., & Singh, N. (2011) · Psychopharmacology · doi:10.1007/s00213-011-2164-0 · Cited by 93 · see citing works
Immunohistochemical localization of plasminogen activator inhibitor-1 in rat and human brain tissues
Hino, H., Akiyama, H., Iseki, E., Kato, M., Kondo, H., Ikeda, K., & Kosaka, K. (2001) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01679-7 · Cited by 55 · see citing works
Local uptake of 14C‐labeled acetate and butyrate in rat brain in vivo during spreading cortical depression
Dienel, G. A., Liu, K., & Cruz, N. F. (2001) · Journal of Neuroscience Research · doi:10.1002/jnr.10063 · Cited by 53 · see citing works
AMYLOID β PEPTIDES STIMULATE TISSUE-TYPE PLASMINOGEN ACTIVATOR BUT NOT RECOMBINANT PROUROKINASE
Wnendt, S., Wetzels, I., & Günzler, W. A. (1997) · Thrombosis Research · doi:10.1016/s0049-3848(97)00006-6 · Cited by 45 · see citing works
Transforming Growth Factor-β1—Modulated Cerebral Gene Expression
Lesné, S., Blanchet, S., Docagne, F., Liot, G., Plawinski, L., MacKenzie, E. T., Auffray, C., Buisson, A., Piétu, G., & Vivien, D. (2002) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200209000-00009 · Cited by 25 · see citing works
Proteolysis in Alzheimer's disease
Periz, G., & Fortini, M. (2000) · EMBO Reports · doi:10.1093/embo-reports/kvd124 · Cited by 21 · see citing works
The TGF‐β1/Upstream Stimulatory Factor‐Regulated PAI‐1 Gene:Potential Involvement and a Therapeutic Target in Alzheimer′sDisease
Higgins, P. J. (2006) · BioMed Research International · doi:10.1155/jbb/2006/15792 · Cited by 15 · see citing works
Untitled work
Zujovic (2000) · doi:10.1002/(sici)1098-1136(20000215)29:4

Flagged first, then by citations

Research works printed but not linked: 1

[18]Flavin MP Zhao G Ho LT Microglial tissue plasminogen activator (tPA) triggers neuronal apoptosis in vitro Glia 2000 29 347 354 10652444

Sorted by citations

Crosstalk between small-cell lung cancer cells and astrocytes mimics brain development to promote brain metastasis
Qu, F., Brough, S. C., Michno, W., Madubata, C. J., Hartmann, G. G., Puno, A., Drainas, A. P., Bhattacharya, D., Tomasich, E., Lee, M. C., et al. (2023) · Nature Cell Biology · doi:10.1038/s41556-023-01241-6 · Cited by 101 · see citing works
HDAC8 cooperates with SMAD3/4 complex to suppress SIRT7 and promote cell survival and migration
Tang, X., Li, G., Su, F., Cai, Y., Shi, L., Meng, Y., Liu, Z., Sun, J., Wang, M., Qian, M., et al. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa039 · Cited by 91 · see citing works
Natural genetic variation determines microglia heterogeneity in wild-derived mouse models of Alzheimer’s disease
Yang, H. S., Onos, K. D., Choi, K., Keezer, K. J., Skelly, D. A., Carter, G. W., & Howell, G. R. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108739 · Cited by 69 · see citing works
Small molecules inhibitors of plasminogen activator inhibitor-1 – An overview
Rouch, A., Vanucci‐Bacqué, C., Bedos‐Belval, F., & Baltas, M. (2015) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2015.01.010 · Cited by 63 · see citing works
Discovery of gene-gene interactions across multiple independent data sets of late onset Alzheimer disease from the Alzheimer Disease Genetics Consortium
Hohman, T. J., Bush, W. S., Jiang, L., Brown-Gentry, K. D., Torstenson, E. S., Dudek, S. M., Mukherjee, S., Naj, A., Kunkle, B. W., Ritchie, M. D., et al. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.10.031 · Cited by 52 · see citing works
Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease
Huang, Y., Wang, M., Ni, H., Zhang, J., Li, A., Hu, B., Junqueira Alves, C., Wahane, S., Rios de Anda, M., Ho, L., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01664-w · Cited by 42 · see citing works
“Of interest in the context of AD was also the downregulation of SerpinE1 (plasminogen activator inhibitor), whose inhibition has been proposed as a therapeutic strategy to reduce amyloid load 49 .”
Synergy between plasminogen activator inhibitor-1, α-synuclein, and neuroinflammation in Parkinson’s disease
Reuland, C. J., & Church, F. (2020) · Medical Hypotheses · doi:10.1016/j.mehy.2020.109602 · Cited by 40 · see citing works
Alzheimer Disease Pathogenesis: The Role of Autoimmunity
Lim, B., Prassas, I., & Diamandis, E. P. (2020) · The Journal of Applied Laboratory Medicine · doi:10.1093/jalm/jfaa171 · Cited by 35 · see citing works
The key genes, phosphoproteins, processes, and pathways affected by efavirenz‐activated CYP46A1 in the amyloid‐decreasing paradigm of efavirenz treatment
Petrov, A. M., Mast, N., Li, Y., & Pikuleva, I. A. (2019) · The FASEB Journal · doi:10.1096/fj.201900092r · Cited by 31 · see citing works
Review of evidence implicating the plasminogen activator system in blood-brain barrier dysfunction associated with Alzheimer’s disease
Tang, M.-Y., Gorin, F. A., & Lein, P. J. (2022) · Ageing and Neurodegenerative Diseases · doi:10.20517/and.2022.05 · Cited by 20 · see citing works
Analysis of immune-related key genes in Alzheimer’s disease
Wu, Y., Liang, S., Zhu, H., & Zhu, Y. (2021) · Bioengineered · doi:10.1080/21655979.2021.1999553 · Cited by 20 · see citing works
Putative autoantibodies in the cerebrospinal fluid of Alzheimer’s disease patients
Lim, B., Tsolaki, M., Batruch, I., Anastasiou, A., Frontistis, A., Prassas, I., & Diamandis, E. P. (2019) · F1000Research · doi:10.12688/f1000research.21140.1 · Cited by 16 · see citing works
Adipose-Derived Molecules–Untouched Horizons in Alzheimer’s Disease Biology
Pichiah, P. B. T., Sankarganesh, D., Arunachalam, S., & Achiraman, S. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00017 · Cited by 16 · see citing works
Pharmacological inhibition of plasminogen activator inhibitor-1 prevents memory deficits and reduces neuropathology in APP/PS1 mice
Rodríguez, G., Eren, M., Haupfear, I., Viola, K. L., Cline, E. N., Miyata, T., Klein, W. L., Vaughan, D. E., & Dong, H. (2023) · Psychopharmacology · doi:10.1007/s00213-023-06459-8 · Cited by 12 · see citing works
An Integrative Transcriptomic Analysis for Identifying Novel Target Genes Corresponding to Severity Spectrum in Spinal Muscular Atrophy
Chung-Wei, Y., Chen, C., Chou, W., Lin, H.-C., Jong, Y., Tsai, L., & Chuang, C. (2016) · PLoS ONE · doi:10.1371/journal.pone.0157426 · Cited by 12 · see citing works
Hypoglycemia, Vascular Disease and Cognitive Dysfunction in Diabetes: Insights from Text Mining-Based Reconstruction and Bioinformatics Analysis of the Gene Networks
Saik, O. V., & Klimontov, V. V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212419 · Cited by 14 · see citing works
A deep phenotyping study in mouse and iPSC models to understand the role of oligodendroglia in optic neuropathy in Wolfram syndrome
Ahuja, K., Vandenabeele, M., Nami, F., Lefevere, E., hoecke, J. V., Bergmans, S., Claes, M., Vervliet, T., Neyrinck, K., Burg, T., et al. (2024) · Acta Neuropathologica Communications · doi:10.1186/s40478-024-01851-7 · Cited by 11 · see citing works
Integrative multi‐omics approaches identify molecular pathways and improve Alzheimer's disease risk prediction
Venkatesh, R., Cardone, K. M., Bradford, Y., Moore, A. K., Kumar, R., Moore, J. H., Shen, L., Kim, D., & Ritchie, M. D. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70886 · Cited by 11 · see citing works
REMOVED: Alzheimer's disease neuropathology is exacerbated following traumatic brain injury. Neuroprotection by co-administration of nanowired mesenchymal stem cells and cerebrolysin with monoclonal antibodies to amyloid beta peptide
Sharma, H. S., Muresanu, D. F., Nozari, A., Lafuente, J. V., Buzoianu, A. D., Sahib, S., Tian, Z. R., Bryukhovetskiy, I., Manzhulo, I., Menon, P. K., et al. (2021) · Progress in brain research · doi:10.1016/bs.pbr.2021.04.008 · Cited by 11 · see citing works
Genetic Variants Associated With Alzheimer Disease in the 22 Arab Countries
Al-Thani, H. F., Ahmad, M. N., Younes, S. N., & Zayed, H. (2021) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000447 · Cited by 11 · see citing works
LC-MS/MS-based serum proteomics reveals a distinctive signature in a rheumatoid arthritis mouse model after treatment with mesenchymal stem cells
Jung, N., Park, S., Kong, T., Park, H., Seo, W. M., Lee, S., & Kang, K. (2022) · PLoS ONE · doi:10.1371/journal.pone.0277218 · Cited by 5 · see citing works
Neuronal mimicry generates an ecosystem critical for brain metastatic growth of SCLCPreprint
Qu, F., Cao, S., Michno, W., Madubata, C. J., Puno, A., Drainas, A. P., Lee, M. C., Yang, D., Toland, A. M. S., Kong, C. S., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.08.10.455426 · Cited by 5 · see citing works
Molecular and Functional Analysis of TLR 1, 2 and 6 in Peripheral Blood Monocytes of Patients with Schizophrenia: A Pilot Study
Sotelo-Ramírez, C. E., Valdés‐Tovar, M., Zaragoza-Hoyos, J. U., Ortíz‐López, L., Argueta, J., Rosel-Vales, M., Miranda-Labra, R. U., & Camarena, B. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26030926 · Cited by 4 · see citing works
Elevated expression of urokinase plasminogen activator in rodent models and patients with cerebral amyloid angiopathy
Vervuurt, M., Zhu, X., Schrader, J. M., de Kort, A. M., Marques, T. M., Kersten, I., van Ton, A. M. P., Abdo, W. F., Schreuder, F. H. B. M., Rasing, I., et al. (2022) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12804 · Cited by 4 · see citing works
Sulodexide and Alzheimer’s Disease: A Preliminary Prospective Study
Lasierra-Cirujeda, J., Pascual-Salcedo, M. J. A., & Aza‐Pascual‐Salcedo, M. (2016) · World Journal of Cardiovascular Diseases · doi:10.4236/wjcd.2016.62007 · Cited by 4 · see citing works
Transcriptional Profile of HIV-induced Nuclear Translocation of Amyloid β in Brain Endothelial Cells
Andras, I. E., Rampersaud, E., Eum, S. Y., & Toborek, M. J. (2014) · Archives of Medical Research · doi:10.1016/j.arcmed.2014.11.003 · Cited by 2 · see citing works
Aging: Thromboembolic Disease, Metabolic Syndrome, Type 2 Diabetes Mellitus, and Alzheimer’s Disease
Lasierra-Cirujeda, J., Pascual-Salcedo, M. J. A., Lasierra-Ibañez, A., AZA, C. L., & Aza‐Pascual‐Salcedo, M. (2016) · Journal of Biosciences and Medicines · doi:10.4236/jbm.2016.45001 · Cited by 2 · see citing works
MicroRNA profiling of the pig periaqueductal grey (PAG) region reveals candidates potentially related to sex-dependent differences
Pawlina‐Tyszko, K., Oczkowicz, M., Gurgul, A., Szmatoła, T., & Bugno‐Poniewierska, M. (2020) · Biology of Sex Differences · doi:10.1186/s13293-020-00343-2 · Cited by 2 · see citing works
Elevated cerebrospinal fluid levels of SERPIN E1 in participants with lewy body diseases
Zimmermann, M., Fandrich, M., Jakobi, M., Röeben, B., Wurster, I., Lerche, S., Schulte, C., Zimmermann, S., Deuschle, C., Schneiderhan‐Marra, N., et al. (2025) · npj Parkinson s Disease · doi:10.1038/s41531-025-00984-3 · Cited by 1 · see citing works
A contemporary review of plasminogen activator inhibitor 1 in cardiovascular disease and broader disease state implications
Becerra, M., Soogoor, N., Vu, J., Wortley, J., & Sathyamoorthy, M. (2026) · Blood Vessels Thrombosis & Hemostasis · doi:10.1016/j.bvth.2026.100141 · Cited by 1 · see citing works
Regulatory roles of rs2192932 and rs10487150 in autism spectrum disorder: insights from fine-mapping and cross-population validation
Zhao, S., Wang, H., Hou, F., Chen, Y., Zhu, K., Liu, R., Xiang, Z., Zhang, J., Liang, X., Li, L., et al. (2025) · Human Molecular Genetics · doi:10.1093/hmg/ddaf107 · Cited by 1 · see citing works
The Physiopathological Crossroads of Aging
Lasierra-Cirujeda, J., Coronel, P., Pascual-Salcedo, M. J. A., Gimeno, M., Salcedo, M. M. A. P., Lasierra-Ibañez, A., & AZA, C. L. (2019) · Journal of Biosciences and Medicines · doi:10.4236/jbm.2019.76007
Integrative assessment of RNA sequencing and in silico analysis to pinpoint mRNAs, lncRNAs, and circRNAs interactions with miRNAs underlying arsenic-induced neurotoxicity
Sarkar, S., Pandey, A. K., Khan, B., & Pant, A. B. (2025) · BMC Genomics · doi:10.1186/s12864-025-11970-7
Impact of genetic variants in the longevity gene PPARGC1A and cerebrospinal fluid PPARγ levels on clinical trajectories in Parkinson's disease: Potential biomarkers for neurodegeneration and ageing
Fandrich, M., Schulte, C., Jakobi, M., Röeben, B., Wurster, I., Lerche, S., Zimmermann, S., Deuschle, C., Schneiderhan‐Marra, N., Joos, T. O., et al. (2026) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2026.108380
Nanocarriers modulating fibrinolytic pathways for the treatment of various neurological disorders
Mishra, K., Tiwari, A. K., Chakradhar, J. V. U. S., Sethi, M., Pandey, S. N., Rana, R., Tripathi, S., Chourasia, M. K., & Chaurasia, M. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-33623-2.00002-7
Gastrodin alleviates mild cognitive impairment and Alzheimer’s disease via candidate targeting of ACHE, S1PR5, SERPINE1, and TOP2A: an integrative computational and cellular study
Wang, Y., Liu, M.-X., Zhu, J.-L., Li, G., Yu, H., Wang, C., Zong, Q., & Wang, W. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1937359

(SERPINE1) Gene Expression in Alzheimer’s Disease
Kutz, S. M., Higgins, C. E., & Higgins, P. J. (2016)
The TGF‐β1/Upstream Stimulatory Factor‐Regulated PAI‐1 Gene:Potential Involvement and a Therapeutic Target in Alzheimer′sDisease
Higgins, P. J. (2006) · BioMed Research International · doi:10.1155/jbb/2006/15792 · Cited by 15 · see citing works
Review Article The TGF-β1/Upstream Stimulatory Factor-Regulated PAI-1 Gene: Potential Involvement and a Therapeutic Target in Alzheimer’s Disease
Higgins, P. J. (2013)
The probable role of tissue plasminogen activator/neuroserpin axis in Alzheimer’s disease: a new perspective
Ali, N. H., Al-Kuraishy, H. M., Al-Gareeb, A. I., Alnaaim, S. A., Alexiou, A. T., Papadakis, M., Saad, ‏. M., & Batiha, G. E. (2023) · Acta Neurologica Belgica · doi:10.1007/s13760-023-02403-x · Cited by 27 · see citing works
Knockout of plasminogen activator inhibitor 1 gene reduces amyloid beta peptide burden in a mouse model of Alzheimer's disease
Liu, R., Groen, T. V., Katre, A. K., Cao, D., Kadisha, I., Ballinger, C. A., Wang, L., Carroll, S. L., & Li, L. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.06.003 · Cited by 95 · see citing works

Authors: M. Kutz, S., E. Higgins, C., & J. Higgins, P.
Venue: Molecular Medicine & Therapeutics
Publisher: OMICS Publishing Group
Published: 2012
Volume: 01
Issue: 02
Pages: 106-106
ISSN: 2324-8769 (ISSN-L)
DOI: 10.4172/2324-8769.1000106
PMC: PMC3703665
OpenAlex: W1992301352
Cited by: 36
References: 28
Citations by year: 2026: 4 · 2025: 5 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 6 · 2019: 3 · 2016: 3 · 2015: 2 · 2014: 1
FWCI: 0.64
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Molecular Medicine & Therapeutics (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of General Medical Sciences (R01GM057242)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: Alzheimer's disease, plasminogen activator inhibitor-1, SERPINE1, amyloid-beta deposition, amyloid precursor protein, TGF-β1, histone deacetylase inhibitors, small molecule drugs, neurodegeneration

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Novel Combinatorial Therapeutic Targeting of PAI-1(SERPINE1) Gene Expression in Alzheimer’s Disease

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks