The cell cycle as a therapeutic target for Alzheimer's disease
Abstract
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease worldwide. It is a progressive, incurable disease whose predominant clinical manifestation is memory loss, and which always ends in death. The classic neuropathological diagnostic markers for AD are amyloid plaques and neurofibrillary tangles, but our understanding of the role that these features of AD play in the etiology and progression of the disease remains incomplete. Research over the last decade has revealed that cell cycle abnormalities also represent a major neuropathological feature of AD. These abnormalities appear very early in the disease process, prior to the appearance of plaques and tangles. Growing evidence suggests that neuronal cell cycle regulatory failure, leading to apoptosis, may be a significant component of the pathogenesis of AD. A number of signaling pathways with the potential to activate aberrant cell cycle re-entry in AD have been described. The relationships among these signaling cascades, which involve the amyloid precursor protein (APP), cyclin-dependent kinases (cdks), and the cell cycle protein Pin1, have not yet been fully elucidated, but details of the individual pathways are beginning to emerge. This review summarizes the current state of knowledge with respect to specific neuronal signaling events that are thought to underlie cell cycle regulatory failure in AD brain. The elements of these pathways that represent potential new therapeutic targets for AD are describe…
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A cell cycle regulatory failure occurs in lymphocytes as it was observed in neurons.
“Nevertheless, despite these several defence mechanisms, authors showed a cell cycle regulatory failure in lymphocytes as it was observed in neurons [130–132, 168, 169].”
From PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease (2009) · cites this paper as [132]
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- Authors
- Neve, R. L., & McPhie, D. L.
- Affiliations
- Harvard University (US)
- Corresponding author
- Neve, Rachael L.
- Venue
- Pharmacology & Therapeutics
- Publisher
- Elsevier BV
- Published
- 2006-07
- Volume
- 111
- Issue
- 1
- Pages
- 99-113
- ISSN
- 0163-7258 (ISSN-L)
- OpenAlex
- W2021459140
- Cited by
- 92
- References
- 9
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 5 · 2020: 5 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 4 · 2013: 6 · 2012: 4
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG021185, AG12954, AG021185, R01AG012954)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, cell cycle re-entry, neuronal apoptosis, therapeutic target, amyloid precursor protein, cyclin-dependent kinases, Pin1, signaling pathways, neurodegeneration, amyloid plaques, neurofibrillary tangles
- MeSH terms
- NIMA-Interacting Peptidylprolyl Isomerase, Alzheimer Disease, Animals, Cell Cycle, Humans, Nerve Degeneration, Signal Transduction, Amyloid beta-Protein Precursor, Cyclin-Dependent Kinases, Peptidylprolyl Isomerase, PPAR gamma
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