파킨슨병 모델 신경세포에서 DJ-1 의 미토콘드리아-소포체 교신 조절 연구

Abstract

Parkinson’s disease (PD) is the second-most common neurodegenerative disease in the world. PD patients show movement defects including resting tremor, bradykinesia, and imbalanced gating. Despite extensive efforts to solve mechanisms underlying PD pathogenesis, there is currently no cure for PD emphasizing various approaches are needed to clarify PD pathogenesis. In a previous study, measurement of Ca2+ level and content around mitochondria-associated ER membrane (MAM) revealed distinctive MAM environments in human alpha-synuclein (α-Syn) A53T mutant overexpressed mouse (SNCA_A53T) neurons. By assessing subcellular Ca2+ dynamics, MAM Ca2+ level, and MAM content, we examined SNCA_A53T neuron-specific MAM environments to gain insight into the pathophysiology of PD. Because accumulating research indicated DJ-1 could interact with α-Syn and suppress its pathological characteristics, we utilized DJ-1 to see whether it could rescue SNCA_A53T neuron- specific MAM environments. This study showed that SNCA_A53T neuron-specific Ca2+ dynamics, MAM Ca2+ level, and MAM content could all be restored by overexpressed DJ-1. Moreover, using different DJ-1 mutants, we were able to obtain clues about the mechanism underlying how pathogenic α-Syn generates SNCA_A53T neuron-specific MAM environments.