The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
GSK-3 is essential in the pathogenesis of Alzheimer's disease
Abstract
Glycogen synthase kinase-3 (GSK-3) is a pivotal molecule in the development of Alzheimer's disease (AD). GSK-3beta is involved in the formation of paired helical filament (PHF)-tau, which is an integral component of the neurofibrillary tangle (NFT) deposits that disrupt neuronal function, and a marker of neurodegeneration in AD. GSK-3beta has exactly the same oligonucleotide sequence as tau-protein kinase I (TPKI), which was first purified from the microtubule fraction of bovine brain. Initially, we discovered that GSK-3beta was involved in amyloid-beta (Abeta)-induced neuronal death in rat hippocampal cultures. In the present review, we discuss our initial in vitro results and additional investigations showing that Abeta activates GSK-3beta through impairment of phosphatidylinositol-3 (PI3)/Akt signaling; that Abeta-activated GSK-3beta induces hyperphosphorylation of tau, NFT formation, neuronal death, and synaptic loss (all found in the AD brain); that GSK-3beta can induce memory deficits in vivo; and that inhibition of GSK-3alpha (an isoform of GSK-3beta) reduces Abeta production. These combined results strongly suggest that GSK-3 activation is a critical step in brain aging and the cascade of detrimental events in AD, preceding both the NFT and neuronal death pathways. Therefore, therapeutics targeted to inhibiting GSK-3 may be beneficial in the treatment of this devastating disease.
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Cites
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864
Glycogen synthase kinase-3β regulates cyclin D1 proteolysis and subcellular localization
Diehl, J. A., Cheng, M., Roussel, M. F., & Sherr, C. J. (1998) · Genes & Development · doi:10.1101/gad.12.22.3499 · Cited by 2,130
IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice
Holzenberger, M., Dupont, J., Ducos, B., Leneuve, P., Géloën, A., Even, P. C., Cervera, P., & Le Bouc, Y. (2003) · Nature · doi:10.1038/nature01298 · Cited by 2,109
Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease
Gómez‐Isla, T., Hollister, R., West, H., Mui, S., Growdon, J. H., Petersen, R. C., Parisi, J. E., & Hyman, B. T. (1997) · Annals of Neurology · doi:10.1002/ana.410410106 · Cited by 1,489
Silva, A. J., Kogan, J. H., Frankland, P. W., & Kida, S. (1998) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.21.1.127 · Cited by 1,462
Diagnostic Criteria for Neuropathologic Assessment of Alzheimer’s Disease
Braak, H., & Braak, E. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00062-6 · Cited by 410
Ishiguro, K., Shiratsuchi, A., Sato, S., Omori, A., Arioka, M., Kobayashi, S., Uchida, T., & Imahori, K. (1993) · FEBS Letters · doi:10.1016/0014-5793(93)81066-9 · Cited by 402
GSK-3β inhibition reverses axonal transport defects and behavioural phenotypes in Drosophila
Mudher, A., Shepherd, D., Newman, T. A., Mildren, P., Jukes, J. P., Squire, A., Mears, A., Berg, S., MacKay, D., Asuni, A. A., et al. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001483 · Cited by 265
Takashima, A., Noguchi, K., Michel, G., Mercken, M., Hoshi, M., Ishiguro, K., & Imahori, K. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(95)12257-5 · Cited by 260
Self-citationLovestone, S., Hartley, C. L., Pearce, J., & Anderton, B. H. (1996) · Neuroscience · doi:10.1016/0306-4522(96)00126-1 · Cited by 201
Cited by
Querfurth, H. W., & LaFerla, F. M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0909142 · Cited by 4,569
Deficient brain insulin signalling pathway in Alzheimer's disease and diabetes
Liu, Y., Liu, F., Grundke‐Iqbal, I., Iqbal, K., & Gong, C. (2011) · The Journal of Pathology · doi:10.1002/path.2912 · Cited by 502
TFEB and TFE3: Linking Lysosomes to Cellular Adaptation to Stress
Raben, N., & Puertollano, R. (2016) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-111315-125407 · Cited by 437
Microtubule-associated protein tau in development, degeneration and protection of neurons
Wang, J.-Z., & Liu, F. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2008.03.002 · Cited by 398
Tau exon 10 alternative splicing and tauopathies
Liu, F., & Gong, C.-X. (2008) · Molecular Neurodegeneration · doi:10.1186/1750-1326-3-8 · Cited by 323
Metadata
- Authors
- Takashima, A.
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2006-07-27
- Volume
- 9
- Issue
- s3
- Pages
- 309-317
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W328531019
- Cited by
- 396
- References
- 11
- FWCI
- 11.96
- Type
- journal article
- Language
- en
- Open access
- closed
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