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Autophagy and programmed cell death—including pyroptosis, apoptosis, and ferroptosis—regulate neuronal integrity and brain aging. The gut microbiota can modulate these pathways, while probiotic interventions act as modulators of autophagic flux and cell-death signaling, supporting neuronal survival. This review outlines probiotic impacts on molecular regulators (Bcl-2 family proteins, caspases, oxidative stress mediators) and examines metabolite-driven effects on neuroinflammation, mitochondrial function, and epigenetic changes, highlighting non-invasive adjunctive potential.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/targeting-autophagy-and-programmed-cell-death-in-neurological-diseases-via-probiotic-intervention/435020/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/targeting-autophagy-and-programmed-cell-death-in-neurological-diseases-via-probiotic-intervention/435020.png","ImageObject",300,407,{"name":92,"@type":93},"Aran","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-08","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why are autophagy and programmed cell death central to neurodegenerative diseases?","Question",{"text":113,"@type":114},"They coordinately determine whether cells survive or are eliminated. 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Gut Pathogens (2026) 18:2 [https://doi.org/10.1186/s13099-025-00787-0](https://doi.org/10.1186/s13099-025-00787-0)  \nGut Pathogens  \nREVIEW Open Access  \nTargeting autophagy and programmed cell death in neurological diseases via probiotic intervention  \nLei Chen 1, Sima-sadat Sabihi2* and Chaoqun Zhang3*  \nAbstract  \nThe 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.  \nKeywords Probiotics, Autophagy, Programmed cell death, Neurodegenerative diseases, Aging  \n*Correspondence:  \nSima-sadat Sabihi  \n[simasadatsabihi1365@outlook.com](simasadatsabihi1365@outlook.com)  \nChaoqun Zhang  \n[zcqjcw@163.com](zcqjcw@163.com)  \n1Department of Neurology, Yongjia People’s Hospital,  \nWenzhou, Zhejiang 325100, China  \n2Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran  \n3Department of Neurology, Tiantai People’s Hospital of Zhejiang Province, Tiantai Branch of Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Taizhou, Zhejiang, China  \nIntroduction  \nAging is the strongest risk factor for major neurodegenerative diseases (NDs), including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. As individuals age, progressive declines in proteostasis, mitochondrial function, and immune regulation increase neuronal vulnerability and promote the accumulation of toxic proteins and damaged organelles. These age-related alterations create a cellular environment in which the mechanisms maintaining neuronal homeostasis become increasingly compromised, ultimately contributing to the onset and progression of NDs. Aging is not a disease but is the main risk factor for major neurodegenerative  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your inten","cbCaibmugfd4h9gV","https://ap.wps.com/l/cbCaibmugfd4h9gV","pdf",1593913,16,"English","# Abstract\n# Keywords\n# Introduction\n## Aging as a risk factor for neurodegenerative diseases\n## Autophagy and programmed cell death in aging\n## Gut–brain axis and microbiome dysbiosis","[{\"question\":\"Why are autophagy and programmed cell death central to neurodegenerative diseases?\",\"answer\":\"They coordinately determine whether cells survive or are eliminated. With aging, autophagic flux declines and multiple PCD pathways become dysregulated, promoting chronic inflammation, oxidative stress, and neuronal loss.\"},{\"question\":\"How do probiotics influence autophagy and programmed cell death signaling?\",\"answer\":\"Probiotic interventions modulate autophagic flux and cell-death signaling. Specific probiotics affect molecular regulators such as Bcl-2 family proteins and caspases and can help restore cellular balance to promote neuronal survival.\"},{\"question\":\"What role does the gut–brain axis play in these mechanisms?\",\"answer\":\"Aging and neurodegenerative diseases are associated with gut microbiota dysbiosis, increased gut permeability, and altered microbial metabolites. These changes can exacerbate neuroinflammation, disrupt mitochondrial function, and modulate autophagy and programmed cell death pathways in the central nervous system.\"}]","Targeting autophagy and programmed cell death in neurological diseases via probiotic intervention | PDF",1790671470]