Targeting autophagy and programmed cell death in neurological diseases via probiotic intervention

Abstract

The progressive degeneration in neuroprotection and cellular homeostasis related to aging significantly contributes to the beginning and development of neurodegenerative diseases (NDs) such as Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease. Autophagy as well as programmed cell death (PCD)—such as pyroptosis, apoptosis, and ferroptosis—play central roles in maintaining neuronal integrity and regulating brain aging. Recent discoveries underscore the essential function of the gut microbiota in modulating these pathways, with probiotic interventions emerging as promising modulators of autophagic flux and cell death signaling. This review explores the intricate crosstalk between probiotics, autophagy, and PCD mechanisms in the context of neurodegenerative diseases and aging. We highlight the capability of specific probiotics to influence molecular regulators such as Bcl-2 family proteins, caspases, and oxidative stress mediators, thereby restoring cellular balance and promoting neuronal survival. Additionally, we examine how probiotics metabolites act as signaling molecules that influence neuroinflammation, mitochondrial function, and epigenetic modifications. Emerging evidence supports the concept that probiotics may serve as non-invasive, adjunctive therapeutic agents capable of mitigating neurodegeneration by modulating autophagic and apoptotic responses. Understanding these mechanistic underpinnings paves the way for innovative microbiota-based involvements aimed at stimulating healthy brain aging and delaying the development of NDs. © The Author(s) 2025.