期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 37, 期 3, 页码 483-494出版社
IOS PRESS
DOI: 10.3233/JAD-130503
关键词
Alzheimer's disease; frontotemporal dementia; nucleus; protein phosphatase 2A; SFPQ; tau; transcription factor
资金
- Australian Research Council
- National Health and Medical Research Council of Australia
This review is dedicated to Inge Grundke-Iqbal who laid the foundations of the tau field, by isolating tau from the Alzheimer's disease (AD) brain, discovering that tau is hyperphosphorylated, and proving a critical role of protein phosphatase 2A (PP2A) and its endogenous inhibitor I-2 (PP2A) in this process. This memorial starts with a few personal notes, and then covers how subcellular fractionation helped in isolating tau. We review in detail the role of PP2A and its endogenous inhibitor in tau phosphorylation. We discuss the role that methylation and phosphorylation have in regulating PP2A activity. We add what we have contributed to understanding the role of tau and PP2A in AD using PP2A transgenic and knockout models, and conclude by addressing two underexplored areas in tau research: tau's non-canonical functions and the role distinct tau isoforms have in a physiological context.
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