Possible Involvement of Genes Related to Lysosomal Storage Disorders in the Pathogenesis of Parkinson’s Disease

Abstract

Parkinson’s disease (PD) characterized with slow continuous degeneration of dopaminergic neurons in the substantia nigra is one of the most common neurodegenerative diseases, but its etiology and pathogenesis are not fully understood. The pathogenesis of PD involves the impairment of lysosomal autophagy, which also contributes to lysosomal storage disorders (LSDs). In this work, the expression of genes related to lysosomal autophagy: Hspa8, Lamp2, Tfam, Slc18a2, and Vps35, was analyzed in the brain tissues of mice with the earliest stage of MPTP-induced PD. The detected decrease in Hspa8 and Lamp2 mRNA levels suggests that dysfunction of lysosomal autophagy may be involved in the earliest stages of PD pathogenesis. A decrease in the rate of lysosomal autophagy may affect the accumulation of damaged proteins and the formation of protein inclusions in PD. Genes related to the lysosome function may be involved in development of both LSD and PD at the earliest stages of these pathophysiological processes.