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Current treatments can only relieve disease symptoms but cannot delay the disease progression. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid traditionally used in hepatology, has recently gained attention for its neuroprotective properties. This review critically evaluates UDCA's mechanisms of action, including the restoration of mitochondrial function, inhibition of apoptosis, reduction of oxidative stress and neuroinflammation, and enhancement of autophagy in both PD and AD models. In vitro and in vivo studies demonstrate UDCA's ability to preserve neuronal integrity, improve motor and cognitive outcomes, and reduce toxic protein aggregates. Although early\u2010phase clinical trials, such as the UDCA for Parkinson's (UP) study in PD, show promising mitochondrial benefits and safety, clinical evidence in AD remains limited. Future directions emphasise the need for large\u2010scale trials, personalised medicine, improved central nervous system (CNS) delivery strategies, or dietary interventions to modulate UDCA production from the gut microbiome. While not a first\u2010line treatment, UDCA represents a compelling mitochondrial stabiliser with disease\u2010modifying potential in NDDs.<\/jats:p>","DOI":"10.1002\/nep3.70039","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T07:40:37Z","timestamp":1779090037000},"page":"111-130","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neuroprotective effects of ursodeoxycholic acid in Parkinson's disease and Alzheimer's disease"],"prefix":"10.1002","volume":"4","author":[{"given":"Ashley En Yi","family":"Chong","sequence":"first","affiliation":[{"name":"Division of Applied Biomedical Sciences and Biotechnology, School of Health Sciences IMU University Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7379-6749","authenticated-orcid":false,"given":"Andrew Octavian","family":"Sasmita","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neuroscience University College Cork Cork Ireland"},{"name":"APC Microbiome Ireland University College Cork Cork Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhun Yian","family":"Koh","sequence":"additional","affiliation":[{"name":"Division of Applied Biomedical Sciences and Biotechnology, School of Health Sciences IMU University Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0930-0619","authenticated-orcid":false,"given":"Anna Pick Kiong","family":"Ling","sequence":"additional","affiliation":[{"name":"Division of Applied Biomedical Sciences and Biotechnology, School of Health Sciences IMU University Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjnut.2025.02.010"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhsg.2025.100740"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2025.03.034"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1080752"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-96594-3"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26136203"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26136404"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252413448"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26125827"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26073416"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-020-0593-y"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26136288"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-024-02769-z"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21103443"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1125-6"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10060898"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26136116"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9051231"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/j2010003"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222313113"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells14080582"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/md20100645"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules30132720"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26094343"},{"key":"e_1_2_14_26_1","unstructured":"Parkinson disease.World Health Organization.Accessed June 12 2025.https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/parkinson-disease."},{"key":"e_1_2_14_27_1","unstructured":"Dementia. 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