Autophagy and Tau Protein

Neurofibrillary tangles, which consist of highly phosphorylated tau protein, and senile plaques (SPs) are pathological hallmarks of Alzheimer’s disease (AD). In swollen axons, many autophagic vacuoles are observed around SP in the AD brain. This suggests that autophagy function is disturbed in AD. W...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-07, Vol.22 (14), p.7475
Main Authors: Hamano, Tadanori, Enomoto, Soichi, Shirafuji, Norimichi, Ikawa, Masamichi, Yamamura, Osamu, Yen, Shu-Hui, Nakamoto, Yasunari
Format: Article
Language:English
Subjects:
Alzheimer's disease
Ammonium chloride
amyloid β protein
autophagic vacuoles
Autophagy
Axons
Chloroquine
Clonidine
Curcumin
Homeostasis
Kinases
Lithium
Metformin
mTORC1
Neurofibrillary tangles
Neuromodulation
Nicotinamide
Phagocytosis
Phosphatase
Phosphorylation
Physiology
Polymerization
Proteins
Rapamycin
Review
Senile plaques
Signal transduction
Tau protein
Toxicity
Vacuoles
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Summary:Neurofibrillary tangles, which consist of highly phosphorylated tau protein, and senile plaques (SPs) are pathological hallmarks of Alzheimer’s disease (AD). In swollen axons, many autophagic vacuoles are observed around SP in the AD brain. This suggests that autophagy function is disturbed in AD. We used a neuronal cellular model of tauopathy (M1C cells), which harbors wild type tau (4R0N), to assess the effects of the lysosomotrophic agent NH4Cl, and autophagy inhibitors chloroquine and 3 methyladenine (3MA). It was found that chloroquine, NH4Cl and 3MA markedly increased tau accumulation. Thus, autophagy lysosomal system disturbances disturbed the degradation mechanisms of tau protein. Other studies also revealed that tau protein, including aggregated tau, is degraded via the autophagy lysosome system. Phosphorylated and C terminal truncated tau were also reported to disturb autophagy function. As a therapeutic strategy, autophagy upregulation was suggested. Thus far, as autophagy modulators, rapamycin, mTOCR1 inhibitor and its analogues, lithium, metformin, clonidine, curcumin, nicotinamide, bexaroten, and torehalose have been proposed. As a therapeutic strategy, autophagic modulation may be the next target of AD therapeutics.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22147475