期刊
EXPERIMENTAL NEUROLOGY
卷 223, 期 2, 页码 304-310出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2009.08.031
关键词
Alzheimer's disease; Tau; Neurofibrillary tangles; Drug discovery
资金
- NIH [P01 AG09215, P30 AG10124, P01 AG11542, P01 AG14382, P01 AG14449, P01 AG17586, PO1 AG19724, P01 NS-044233, UO1 AG24904]
- Marian S. Ware Alzheimer Program
The microtubule-associated protein tau forms insoluble filaments that deposit as neurofibrillary tangles (NFTs) in the brains of those with Alzheimer's disease (AD) and other related neurodegenerative disorders. The presence of both NFTs and amyloid beta (A beta)-containing senile plaques within the brain is required to confirm the diagnosis of AD. However, the demonstration that familial AD can be caused by mutations that result in increased A beta production has resulted in AD drug discovery strategies that are largely focused on reducing brain A beta levels, with substantially less emphasis on tau-directed approaches. This trend may be changing, as there are an increasing number of research programs that are exploring ways to reduce NFTs in AD and related tauopathies. We briefly review recent advances in tau-based drug discovery, with an emphasis on the identification of compounds that inhibit the assembly of tau into multimers and fibrils. (C) 2009 Elsevier Inc. All rights reserved.
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