{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:18:39Z","timestamp":1787501919268,"version":"build-2736575974"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":67,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100018749","name":"Korea Brain Research Institute","doi-asserted-by":"publisher","award":["KBRI 26-BR-01-02"],"award-info":[{"award-number":["KBRI 26-BR-01-02"]}],"id":[{"id":"10.13039\/100018749","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["PM2024ST0018"],"award-info":[{"award-number":["PM2024ST0018"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Brain"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Parkinson\u2019s disease (PD) is the second most prevalent neurodegenerative disorder worldwide. Although various therapeutics have been developed, no disease-modifying treatment has been established to date. Recent studies highlight critical roles of p21-activated protein kinases (PAKs) in the pathogenesis of PD. To investigate the potential of PAK1 as a therapeutic target for PD, we examined the effects of a constitutively active form of PAK1 (PAK1-T423E; PAK1-CA) in animal models. An animal model of PD, recapitulating \u03b1-synucleinopathy was established by injecting human \u03b1-synuclein preformed fibrils into the biceps femoris of M83 A53T homozygous mice. PAK1-CA expression significantly ameliorated behavioral deficits and prevented the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Moreover, PAK1-CA expression increased the survival rate, although it was not significant in this model. In contrast, in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxin model, PAK1-CA expression significantly improved survival rates compared to the GFP-expressing control group. These findings suggest a potential role for constitutively active PAK1 in contributing to the neuroprotection of dopaminergic neurons, which may imply its utility as a candidate for gene therapy.<\/jats:p>","DOI":"10.1186\/s13041-026-01320-3","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T04:15:53Z","timestamp":1781151353000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["PAK1 expression protects cellular and behavioral defects in animal models of Parkinson\u2019 s disease"],"prefix":"10.1186","volume":"19","author":[{"given":"Jeong Eun","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kina","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Jeong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won-Jong","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyong Kyu","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"issue":"12","key":"1320_CR1","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1038\/s41582-024-01034-x","volume":"20","author":"F Stocchi","year":"2024","unstructured":"Stocchi F, Bravi D, Emmi A, Antonini A. 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