{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T16:42:05Z","timestamp":1788280925559,"version":"build-2803163510"},"reference-count":187,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Inner Mongolia Autonomous Region of China","award":["2021MS08082"],"award-info":[{"award-number":["2021MS08082"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Parkinson\u2019s disease (PD), the world\u2019s second most prevalent neurodegenerative disorder, is characterized by progressive neuronal degeneration mediated through intricate pathological mechanisms. Phosphorylation signaling pathways have been increasingly recognized as critical modulators in the development and progression of PD. Meanwhile, short-chain fatty acids (SCFAs), primarily produced by gut microbiota, have shown considerable neuroprotective potential by promoting autophagy, alleviating mitochondrial dysfunction, and regulating neuroinflammatory responses. Recent research suggests that SCFAs may influence the phosphorylation dynamics of key signaling pathways, including MAPKs, NF-\u03baB, JAK\/STAT, PI3K\/Akt, AMPK, and Nrf2\/Keap1\/ARE, thereby modulating disease pathophysiology. This review aims to systematically evaluate how SCFAs modulate phosphorylation pathways to influence neuroinflammation, \u03b1-synuclein aggregation, and mitochondrial dysfunction in PD. By investigating this issue, we identify potential molecular targets and propose future research directions, offering new insighreviewts and strategies for the development of novel therapeutic and preventive interventions for PD.<\/jats:p>","DOI":"10.7717\/peerj.20688","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T08:45:28Z","timestamp":1769589928000},"page":"e20688","source":"Crossref","is-referenced-by-count":2,"title":["Deciphering the modulatory role of short-chain fatty acids in Parkinson\u2019s disease\n                    <i>via<\/i>\n                    phosphorylation-dependent signaling mechanisms"],"prefix":"10.7717","volume":"14","author":[{"given":"Jiaji","family":"Liu","sequence":"first","affiliation":[{"name":"Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruijun","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Hohhot First Hospital, Hohhot, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4443","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"issue":"2","key":"10.7717\/peerj.20688\/ref-1","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/j.bbadis.2016.11.005","article-title":"Nrf2 signaling pathway: pivotal roles in inflammation","volume":"1863","author":"Ahmed","year":"2017","journal-title":"Biochimica et Biophysica Acta (BBA)\u2014Molecular Basis of Disease"},{"issue":"1","key":"10.7717\/peerj.20688\/ref-2","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s13024-021-00427-6","article-title":"Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson\u2019s disease","volume":"16","author":"Aho","year":"2021","journal-title":"Molecular Neurodegeneration"},{"issue":"5","key":"10.7717\/peerj.20688\/ref-3","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1111\/jnc.14808","article-title":"\u03b1-synuclein oligomers and fibrils: a spectrum of species, a spectrum of toxicities","volume":"150","author":"Alam","year":"2019","journal-title":"Journal of Neurochemistry"},{"issue":"40","key":"10.7717\/peerj.20688\/ref-4","doi-asserted-by":"publisher","first-page":"29739","DOI":"10.1074\/jbc.M600933200","article-title":"Phosphorylation of ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic lewy body disease","volume":"281","author":"Anderson","year":"2006","journal-title":"Journal of Biological Chemistry"},{"issue":"2","key":"10.7717\/peerj.20688\/ref-5","doi-asserted-by":"publisher","first-page":"271","DOI":"10.3892\/ijmm.2017.3036","article-title":"The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (review)","volume":"40","author":"Ardito","year":"2017","journal-title":"International Journal of Molecular Medicine"},{"issue":"9","key":"10.7717\/peerj.20688\/ref-6","doi-asserted-by":"publisher","first-page":"2348","DOI":"10.1007\/s11064-021-03369-z","article-title":"Neuroprotective effects of sodium butyrate through suppressing neuroinflammation and modulating antioxidant enzymes","volume":"46","author":"Bayazid","year":"2021","journal-title":"Neurochemical Research"},{"issue":"5","key":"10.7717\/peerj.20688\/ref-7","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/j.bbamcr.2018.02.010","article-title":"Nrf2-Keap1 signaling in oxidative and reductive stress","volume":"1865","author":"Bellezza","year":"2018","journal-title":"Biochimica et Biophysica Acta (BBA)\u2014Molecular Cell Research"},{"issue":"10291","key":"10.7717\/peerj.20688\/ref-8","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1016\/S0140-6736(21)00218-X","article-title":"Parkinson\u2019s disease","volume":"397","author":"Bloem","year":"2021","journal-title":"Lancet"},{"key":"10.7717\/peerj.20688\/ref-9","doi-asserted-by":"publisher","first-page":"287","DOI":"10.3389\/fonc.2018.00287","article-title":"\u201cDo We Know Jack\u201d about JAK? 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