DJ-1 in Parkinson's disease: Its important role at endoplasmic reticulum–mitochondria contact sites

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting millions of people globally and causing significant impairments in motor and cognitive functions. The key pathological hallmarks of PD include the aggregation of α-synuclein (α-Syn), degeneration of dopaminergic neurons, and formation of Lewy bodies (LBs), leading to a range of clinical symptoms, such as rigidity, bradykinesia, and cognitive deficits. Although the exact causes of PD are not fully understood, factors such as oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress are implicated in its pathogenesis. The protein DJ-1 (PARK7), a highly conserved antioxidant, has been identified as a significant factor in PD, particularly because of its role in maintaining cellular homeostasis and regulating cellular responses to stress. The interaction of DJ-1 with endoplasmic reticulum–mitochondria contact sites (MERCs) is crucial for calcium regulation, autophagy, and the management of ER stress, all of which are related to PD progression. This review focuses on the function of DJ-1 within mitochondria-associated endoplasmic reticulum membranes (MAMs or ER-MAMs), aiming to provide insights into PD mechanisms and potential therapeutic targets.