The Potential Roles of HSPA2 in Parkinson's Disease

Parkinson's disease (PD) is a neurodegenerative disorder traditionally identified by its characteristic motor symptoms, the presence of Lewy bodies, and the loss of neurons in the substantia nigra. At present, there is no cure for the disease. Our study aimed to uncover the new aspects of the pathogenesis underlying PD. Firstly, we identified that HSPA2 is potentially involved in the PD pathogenesis through a bioinformatic approach; HSPA2 was associated with the disease duration. For that, we analyzed the correlation of the clinical information of patients with the HSPA2 gene expression level. Then, the expression of HSPA2 was investigated in vivo using the midbrain from the MPTP-treated mouse models. The HSPA2 levels significantly increased in the midbrain tissue from the PD mouse models. The mechanistic studies about HSPA2 in the pathogenesis of PD were conducted in vitro in the HEK293T cell line, which observed the changes in α-synuclein expression by regulating the HSPA2 expression. In the HEK293T cell line, the overexpression of HSPA2 increased the α-synuclein aggregates formation, and the knockdown of HSPA2 reduced the α-synuclein aggregates accumulation. Therefore, this study hypothesized that HSPA2 might be a new regulator of α-synuclein associated with the PD pathology.