Brain Disorders (Sep 2021)
DJ-1 and Parkinson's disease
Abstract
Parkinson's disease (PD) is characterized by a significant loss in movement, tremors, and impaired posture. Worldwide prevalence of PD indicates that aging increases the risk of PD development and is more common in males than females. Several environmental factors along with potential genetic factors have been found to affect the development of PD. Most common finding in PD is degeneration of the dopamine-producing (dopaminergic) neurons within the nigrostriatal pathway, and neuroinflammation due to increased oxidative stress has been associated to trigger the degeneration of these dopaminergic neurons in substantia nigra. Within the substantia nigra, dopaminergic neurons have been well known to produce reactive oxygen species (ROS) that cause overactivation of microglia, which are the major resident immune cells in the brain. The pro-inflammatory cytokines produced by hyperactive microglia lead to significant neuroinflammation and degeneration of neurons. Mutations in several genes also play a large role in the overaccumulation of ROS within these neurons. Among such genes, mutations in the protein DJ-1 encoded by PARK-7 gene cause autosomal recessive forms of PD. Several animal studies have explored DJ-1 as a possible therapeutic target for PD and neurodegeneration, and therefore, human clinical studies that would represent an important step in unravelling the potential of DJ-1 as an ideal target for therapeutic intervention are warranted. This review attempts to describe functions and mutations of DJ-1 and its possible roles in the pathogenesis of PD.
