{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T13:06:24Z","timestamp":1779368784826,"version":"3.53.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T00:00:00Z","timestamp":1665014400000},"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. Mol. Neurosci."],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of midbrain dopaminergic neurons. The miR-29s family, including <jats:italic>miR-29a<\/jats:italic> and <jats:italic>miR-29b1<\/jats:italic> as well as <jats:italic>miR-29b2<\/jats:italic> and <jats:italic>miR-29c<\/jats:italic>, are implicated in aging, metabolism, neuronal survival, and neurological disorders. In this study, the roles of <jats:italic>miR-29a\/b1<\/jats:italic> in aging and PD were investigated. <jats:italic>miR-29a\/b1<\/jats:italic> knockout mice (named as 29a KO hereafter) and their wild-type (WT) controls were used to analyze aging-related phenotypes. After challenged with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), dopaminergic injuries, glial activation, and mouse behaviors were evaluated. Primary glial cells were further cultured to explore the underlying mechanisms. Additionally, the levels of miR-29s in the cerebrospinal fluid (CSF) of PD patients (<jats:italic>n<\/jats:italic> = 18) and healthy subjects (<jats:italic>n<\/jats:italic> = 17) were quantified. 29a KO mice showed dramatic weight loss, kyphosis, and along with increased and deepened wrinkles in skins, when compared with WT mice. Moreover, both abdominal and brown adipose tissues reduced in 29a KO mice, compared to their WT counterpart. However, in MPTP-induced PD mouse model, the deficiency of <jats:italic>miR-29a\/b1<\/jats:italic> led to less severe damages of dopaminergic system and mitigated glial activation in the nigrostriatal pathway, and subsequently alleviated the motor impairments in 3-month-old mice. Eight-month-old mutant mice maintained such a resistance to MPTP intoxication. Mechanistically, the deficiency of <jats:italic>miR-29a\/b-1<\/jats:italic> promoted the expression of neurotrophic factors in 1-Methyl-4-phenylpyridinium (MPP<jats:sup>+<\/jats:sup>)-treated primary mixed glia and primary astrocytes. In lipopolysaccharide (LPS)-treated primary microglia, knockout of <jats:italic>miR-29a\/b-1<\/jats:italic> inhibited the expression of inflammatory factors, and promoted the expression of anti-inflammatory factors and neurotrophic factors. Knockout of <jats:italic>miR-29a\/b1<\/jats:italic> increased the activity of AMP-activated protein kinase (AMPK) and repressed NF-\u03baB\/p65 signaling in glial cells. Moreover, we found miR-29a level was increased in the CSF of patients with PD. Our results suggest that 29a KO mice display the peripheral premature senility. The combined effects of less activated glial cells might contribute to the mitigated inflammatory responses and elicit resistance to MPTP intoxication in <jats:italic>miR-29a\/b1<\/jats:italic> KO mice.<\/jats:p>","DOI":"10.3389\/fnmol.2022.978191","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T12:43:00Z","timestamp":1665060180000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Deficiency of miR-29a\/b1 leads to premature aging and dopaminergic neuroprotection in mice"],"prefix":"10.3389","volume":"15","author":[{"given":"Xiaochen","family":"Bai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoshuang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilin","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongtao","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaolin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtian","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruilin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Fei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1007\/s10522-020-09865-z","article-title":"Natural anti-aging skincare: Role and potential.","volume":"21","author":"Ahmed","year":"2020","journal-title":"Biogerontology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"5411","DOI":"10.1038\/s41598-017-03887-3","article-title":"Downregulation of blood serum microRNA 29 family in patients with Parkinson\u2019s disease.","volume":"7","author":"Bai","year":"2017","journal-title":"Sci. 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