Senescent microglia are a distinct microglial phenotype present in aging brain that have been implicated in the progression of aging and age-related neurodegenerative diseases. However, the specific mechanisms that trigger microglial senescence are largely unknown. Quinolinic acid (QA) is a cytotoxic metabolite produced upon abnormal activation of microglia. Brain aging and age-related neurodegenerative diseases have an elevated concentration of QA. In the present study, we investigated whether QA promotes aging and aging-related phenotypes in microglia and C. elegans. Here, we demonstrate for the first time that QA, secreted by abnormal microglial stimulation, induces impaired mitophagy by inhibiting mitolysosome formation and consequently promotes the accumulation of damaged mitochondria due to reduced mitochondrial turnover in microglial cells. Defective mitophagy caused by QA drives microglial senescence and poor healthspan in C. elegans. Moreover, oxidative stress can mediate QA-i
Increased quinolinic acid (QA) has been suggested in various mental disease pathology. Excessive QA is shown to overactivate N-Methyl-D-aspartic acid (NMDA) receptor subunit 2B (NR2B) receptors and is deleterious to the neurons; however, the exact mechanism behind this effect is complex and not fully understood. This thesis aimed to investigate the mechanism of QA-induced neurite impairment.
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