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Published on: October 10, 2017
mTor mediates tau localization and secretion: Implication for Alzheimer's disease
Zhi Tang1, Eniko Ioja2, Erika Bereczki2
1Karolinska Institutet, NVS Department, Centrum for Alzheimer Research, Division for Neurogeriatrics, Novum, SE 14186 Stockholm, Sweden; Department of Clinical Laboratory, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China.
Mammalian target of rapamycin (mTor) signaling influences the distribution and phosphorylation of tau protein. Aberrant mTor activity affects tau localization in cellular organelles and its secretion, potentially contributing to Alzheimer's disease pathology.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Abnormal tau hyperphosphorylation forms neurofibrillary tangles, a hallmark of Alzheimer's disease (AD).
- Elevated cerebrospinal fluid (CSF) tau levels are observed in AD patients.
- Aberrant mammalian target of rapamycin (mTor) signaling is implicated in tau hyperphosphorylation.
Purpose of the Study:
- To investigate the role of mTor in the intracellular distribution and secretion of tau.
- To examine the relationship between mTor activity and tau phosphorylation status.
Main Methods:
- Analysis of tau localization in post-mortem human AD brain tissue.
- Study of tau synthesis, distribution, and phosphorylation in human neuroblastoma cells with varying mTor expression.
- Assessment of tau re-localization and secretion under different mTor activity levels.
Main Results:
- Tau was found in various organelles, including mitochondria and endoplasmic reticulum, in human AD brains.
- Altered mTor expression (overexpression or deficiency) in SH-SY5Y cells led to an imbalance of phosphorylated (p-) and non-phosphorylated (Np-) tau.
- Increased mTor activity promoted tau accumulation in the cytoplasm and its secretion via exocytotic vesicles.
Conclusions:
- mTor signaling plays a critical role in regulating tau's subcellular distribution.
- mTor influences the initiation of tau secretion from cells into the extracellular space.
- These findings suggest mTor as a potential therapeutic target for tauopathies like AD.
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