The mechanism of cuproptosis in Parkinson's disease

Abstract

Parkinson's disease (PD) is a neurodegenerative disease with an increased morbidity. The pathogenesis PD has not been fully elucidated, and whatever mechanism is involved, it ultimately leads to dopamine (DA) neuronal apoptosis. Cuproptosis is a novel form of cell death. Its morphology, biochemical properties, and mechanism of action differ from known forms of cell death, such as apoptosis, autophagy, necrosis and pyroptosis. Copper binds to the lipoylated components of the tricarboxylic acid cycle, causing proteotoxic stress that ultimately leads to cellular cuproptosis. PD has biochemical features such as mitochondrial dysfunction and decreased levels of copper and glutathione in brain regions. This is closely related to the cuproptosis mechanism. However, the specific link between the pathogenesis of PD and cuproptosis is unclear. Herein, we summarizes cuproptosis as the cause of DA neuronal death in PD, and the relationship between cuproptosis and the PD pathogenesis. This article provides a research basis for targeted cuproptosis for PD.

Keywords: Copper; Cuproptosis; Dopamine; Glutathione; Parkinson’s disease; α-synuclein.