{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:41:44Z","timestamp":1792075304283,"version":"4.4.0"},"reference-count":298,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is considered the second most common neurodegenerative disease worldwide; treating this disease remains quite challenging. Environmental and genetic factors may play a role in the pathophysiology of PD. \u03b1-synuclein aggregation, oxidative stress, ferroptosis, mitochondrial failure, neuroinflammation, and gut dysbiosis are among the known risk factors of PD. The pathophysiology of Parkinson\u2019s disease is complicated by the interconnections between these molecular pathways, which also present significant obstacles to treatment development. However, due to its complex mechanism and long latency, PD is difficult to diagnose and detect, which presents a barrier to treatment. In addition, the need to develop new treatments for PD is increased by the fact that the majority of traditional therapeutic methods have major side effects and limited effects. Therefore, a deeper understanding of the fundamental mechanisms underlying PD is required. This review provides a comprehensive analysis of the current landscape of PD pathophysiology, paying particular attention to the molecular processes of PD, as well as the traditional research models, clinical diagnostic standards, documented medication therapeutic approaches, and recently disclosed drug candidates in clinical trials. We also highlighted the herbal-derived components that have recently been identified for their effects in the treatment of PD to provide a review and perspectives for the development of the next generation of drugs and preparations for the treatment of PD.<\/jats:p>","DOI":"10.3390\/ijms26136416","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T06:54:16Z","timestamp":1751525656000},"page":"6416","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Parkinson Disease Signaling Pathways, Molecular Mechanisms, and Potential Therapeutic Strategies: A Comprehensive Review"],"prefix":"10.3390","volume":"26","author":[{"given":"Muhammad S.","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Cellular and Integrative Physiology, School of Medicine, University of Texas Health Science Center at San Antonio (UTHSCSA), 7703 Floyd Curl Dr., San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9535-2097","authenticated-orcid":false,"given":"Somayyeh","family":"Nasiripour","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, School of Medicine, University of Texas Health Science Center at San Antonio (UTHSCSA), 7703 Floyd Curl Dr., San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean C.","family":"Bopassa","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, School of Medicine, University of Texas Health Science Center at San Antonio (UTHSCSA), 7703 Floyd Curl Dr., San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,3]]},"reference":[{"key":"ref_1","unstructured":"GBD 2016 Disease and Injury Incidence and Prevalence Collaborators (2017). 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