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PINCH in the cellular stress response to tau-hyperphosphorylation
Ahmet Yunus Ozdemir1, Inna Rom, Jane Kovalevich
1Temple University School of Medicine, Department of Neuroscience, Philadelphia, Pennsylvania, USA.
Plos One
|April 5, 2013
Summary
PINCH protein stabilizes hyperphosphorylated Tau, a key factor in neurodegenerative diseases like Alzheimer's and HIV encephalitis. Reducing PINCH aids in clearing this harmful Tau accumulation.
Area of Science:
- Neuroscience
- Molecular Biology
- Protein Interactions
Background:
- PINCH (particularly interesting new cysteine-histidine-rich protein) is an adaptor protein crucial for neurite extension under stress.
- Previous research linked PINCH to reduced synaptodendritic signaling proteins in Human Immunodeficiency Virus (HIV) patients' brains.
Purpose of the Study:
- To investigate the potential role of PINCH in neurodegenerative diseases.
- To explore the interaction of PINCH with Tau and heat shock proteins.
Main Methods:
- Mass spectrometry to predict protein interactions.
- In vitro experiments to confirm binding of PINCH to hyperphosphorylated Tau and C-terminal binding protein.
- Gene silencing of PINCH to observe its effect on hyperphosphorylated Tau clearance.
- Analysis of brain tissues from patients with HIV encephalitis (HIVE), Alzheimer's disease (AD), and frontotemporal dementia (FTD).
Main Results:
- PINCH was confirmed to bind to hyperphosphorylated Tau and E3 ubiquitin ligase.
- Silencing PINCH enhanced the clearance of hyperphosphorylated Tau, indicating PINCH stabilizes it.
- PINCH levels were elevated and bound to hyperphosphorylated Tau in brain tissues from HIVE, AD, and FTD patients.
Conclusions:
- PINCH plays a role in stabilizing hyperphosphorylated Tau, contributing to its accumulation in neurodegenerative diseases.
- These findings reveal a potential mechanism linking HIV and Alzheimer's disease.
- PINCH is identified as a significant factor in the pathogenesis of diseases characterized by hyperphosphorylated Tau accumulation.
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