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PRE-RECORDED: METABOLIC CHANGES IN MICROGLIA AND THEIR EFFECT ON NEUROTOXICITY IN PARKINSON'S DISEASE
Abstract
Abstract Body
Parkinson's disease (PD) , a neurodegenerative disease, is associated with impairment with motor activity and rigidity. The genetic risks of the disease is reported to be between 5 and 10%. It was suggested that activated microglia may play a role in neurotoxicity to dopaminergic neurons (Lazdon et al JNC 2019). We found that reduction in DJ-1 protein ( found in PD patients) in microglia increase both their pro-inflammatory profile and neurotoxicity. Autophagy is an important mechanism for the degradation of intracellular proteins and organelles. We discovered that impaired DJ-1 microglia exhibit an impaired autophagy-dependent degradation of p62 and LC3 proteins, an important protein in the autophagy flux. We discovered that impaired autophagy affects the ability of DJ-1 microglia to uptake αSyn. Further research suggests that αSyn affects microglia metabolism both in vitro and in vivo, leading to their neurotoxic properties. Targeting those metabolic changes in microglia may lead to new therapeutic avenues in the disease.