Immune cell metabolic dysfunction in Parkinson's disease

Parkinson's disease (PD) is a multi-system disorder characterized histopathologically by degeneration of dopaminergic neurons in the substantia nigra pars compacta. While the etiology of PD remains multifactorial and complex, growing evidence suggests that cellular metabolic dysfunction is a critical driver of neuronal death. Defects in cellular metabolism related to energy production, oxidative stress, metabolic organelle health, and protein homeostasis have been reported in both neurons and immune cells in PD. We propose that these factors act synergistically in immune cells to drive aberrant inflammation in both the CNS and the periphery in PD, contributing to a hostile inflammatory environment which renders certain subsets of neurons vulnerable to degeneration. This review highlights the overlap between established neuronal metabolic deficits in PD with emerging findings in central and peripheral immune cells. By discussing the rapidly expanding literature on immunometabolic dysfunction in PD, we aim to draw attention to potential biomarkers and facilitate future development of immunomodulatory strategies to prevent or delay the progression of PD.