Unknown

Dataset Information

0

"Amyloid-beta accumulation cycle" as a prevention and/or therapy target for Alzheimer's disease.


ABSTRACT: The cell cycle and its regulators are validated targets for cancer drugs. Reagents that target cells in a specific cell cycle phase (e.g., antimitotics or DNA synthesis inhibitors/replication stress inducers) have demonstrated success as broad-spectrum anticancer drugs. Cyclin-dependent kinases (CDKs) are drivers of cell cycle transitions. A CDK inhibitor, flavopiridol/alvocidib, is an FDA-approved drug for acute myeloid leukemia. Alzheimer's disease (AD) is another serious issue in contemporary medicine. The cause of AD remains elusive, although a critical role of latent amyloid-beta accumulation has emerged. Existing AD drug research and development targets include amyloid, amyloid metabolism/catabolism, tau, inflammation, cholesterol, the cholinergic system, and other neurotransmitters. However, none have been validated as therapeutically effective targets. Recent reports from AD-omics and preclinical animal models provided data supporting the long-standing notion that cell cycle progression and/or mitosis may be a valid target for AD prevention and/or therapy. This review will summarize the recent developments in AD research: (a) Mitotic re-entry, leading to the "amyloid-beta accumulation cycle," may be a prerequisite for amyloid-beta accumulation and AD pathology development; (b) AD-associated pathogens can cause cell cycle errors; (c) thirteen among 37 human AD genetic risk genes may be functionally involved in the cell cycle and/or mitosis; and (d) preclinical AD mouse models treated with CDK inhibitor showed improvements in cognitive/behavioral symptoms. If the "amyloid-beta accumulation cycle is an AD drug target" concept is proven, repurposing of cancer drugs may emerge as a new, fast-track approach for AD management in the clinic setting.

SUBMITTER: Rao CV 

PROVIDER: S-EPMC7059149 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

"Amyloid-beta accumulation cycle" as a prevention and/or therapy target for Alzheimer's disease.

Rao Chinthalapally V CV   Asch Adam S AS   Carr Daniel J J DJJ   Yamada Hiroshi Y HY  

Aging cell 20200125 3


The cell cycle and its regulators are validated targets for cancer drugs. Reagents that target cells in a specific cell cycle phase (e.g., antimitotics or DNA synthesis inhibitors/replication stress inducers) have demonstrated success as broad-spectrum anticancer drugs. Cyclin-dependent kinases (CDKs) are drivers of cell cycle transitions. A CDK inhibitor, flavopiridol/alvocidib, is an FDA-approved drug for acute myeloid leukemia. Alzheimer's disease (AD) is another serious issue in contemporary  ...[more]

Similar Datasets

| S-EPMC7566501 | biostudies-literature
| S-EPMC5650911 | biostudies-other
2021-11-24 | PXD025620 | Pride
2015-02-12 | E-GEOD-65851 | biostudies-arrayexpress
2010-05-30 | GSE20447 | GEO
| S-EPMC10298272 | biostudies-literature
| S-EPMC10310781 | biostudies-literature
| S-EPMC7603688 | biostudies-literature
| S-EPMC8162409 | biostudies-literature
| S-EPMC7048875 | biostudies-literature