{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T03:00:40Z","timestamp":1793674840490,"version":"4.5.1"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>As a core driver in the pathological progression of neurological diseases, oxidative stress contributes to the onset and development of multiple disorders, including traumatic brain injury (TBI), Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), Huntington\u2019s disease (HD), and amyotrophic lateral sclerosis (ALS), by inducing interconnected and bidirectional damage among mitochondria, endoplasmic reticulum, lysosomes, and the nucleus. This review systematically summarizes the oxidative stress-mediated inter-organelle crosstalk network: Mitochondria act as one of the earliest and central hubs, and their dysfunction (e.g., reactive oxygen species burst, calcium overload, and respiratory chain impairment) induces endoplasmic reticulum stress via ROS diffusion and calcium signaling disturbance. The disruption of endoplasmic reticulum calcium homeostasis further exacerbates mitochondrial damage, forming a vicious cycle. Lysosomes exhibit reduced membrane stability and impaired autophagic flux under oxidative stress, failing to clear damaged organelles and aggravating oxidative stress accumulation. Ultimately, oxidative stress signals are transmitted to the nucleus, resulting in DNA damage, aberrant epigenetic modifications, and activation of pro-inflammatory\/pro-apoptotic genes, thereby accelerating disease progression. Notably, this organelle injury transmission is not a rigid unidirectional linear cascade; primary lysosomal or MAM defects can independently initiate the full organelle damage loop without preceding mitochondrial dysfunction. This review integrates current studies, clarifies context-dependent and disease-specific characteristics of organelle interactions, and discusses potential therapeutic strategies with critical consideration of translational challenges and limitations, providing a theoretical foundation for mechanistic research and clinical intervention of neurological diseases.<\/jats:p>","DOI":"10.3389\/fnagi.2026.1892923","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:52:00Z","timestamp":1784699520000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Oxidative stress as a driver of organelle cascade damage in neurological diseases"],"prefix":"10.3389","volume":"18","author":[{"given":"Shiwang","family":"Li","sequence":"first","affiliation":[{"name":"School of Clinical Medicine, Qinghai University","place":["Xining, Qinghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taijian","family":"Cao","sequence":"additional","affiliation":[{"name":"Qinghai University Affiliated Hospital","place":["Xining, Qinghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Qinghai Provincial People's Hospital","place":["Xining, Qinghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"105095","DOI":"10.1016\/j.neuint.2021.105095","article-title":"Mitochondrial quality control: epigenetic signatures and therapeutic strategies","volume":"148","author":"Ambekar","year":"2021","journal-title":"Neurochem. 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