DJ-1 can inhibit microtubule associated protein 1 B formed aggregates.

Abstract

BACKGROUND:

Abnormal accumulation and aggregation of microtubule associated proteins (MAPs) plays an important role in the pathogenesis of neurodegenerative diseases. Loss-of-function mutation of DJ-1/Park7 can cause early onset of PD. DJ-1, a molecular chaperone, can inhibit α-synuclein aggregation. Currently, little is known whether or not loss of function of DJ-1 contributes to abnormal MAPs aggregation in neurodegenerative disorders such as PD.

RESULTS:

We presented evidence that DJ-1 could bind to microtubule associated protein1b Light Chain (MAP1b-LC). Overexpression of DJ-1 prevented MAP1b-LC aggregation in HEK293t and SH-SY5Y cells while DJ-1 knocking down (KD) enhanced MAP1b-LC aggregation in SH-SY5Y cells. The increase in insoluble MAP1b-LC was also observed in the DJ-1 null mice brain. Moreover, in the DJ-1 KD SH-SY5Y cells, overexpression of MAP1B-LC led to endoplasmic reticulum (ER) stress-induced apoptosis.

CONCLUSION:

Our results suggest that DJ-1 acts as a molecular chaperone to inhibit MAP1B aggregation thus leading to neuronal apoptosis. Our study provides a novel insight into the mechanisms that underly the pathogenesis of Parkinson's disease (PD).

• Authors: Zhiquan Wang, Yu Zhang, Shi Zhang, Qianqian Guo, Yuyan Tan, Xinyi Wang, Ran Xiong, Jianqing Ding, Shengdi Chen
• Journal: Molecular neurodegeneration (Mol Neurodegener) Vol. 6 Pg. 38 (Jun 06 2011) ISSN: 1750-1326 [Electronic] England
• PMID: 21645326 (Publication Type: Journal Article)