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. These cellular defects led to dopaminergic neurodegeneration, locomotory impairments, and reduced lifespan, establishing succinate as a pro-neurodegenerative and pro-aging metabolite. Transcriptomic and genetic analyses revealed the involvement of nutrient-sensing pathways, prominently mTORC1, in promoting proteotoxic stress. Together, these findings highlight a direct link between microbial metabolism, proteostasis collapse, and neurodegeneration, establishing succinate as an active modulator of aging. Targeting succinate signaling mechanisms may therefore represent a tractable strategy for microbiome-based interventions in Parkinson's disease and age-associated neurodegeneration.
Akbar et al. (Fri,) studied this question.