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It is demonstrated that the FHFs subfamily plays cardinal roles in several neuropathological diseases, while their involvement in Parkinson's disease (PD) has been so far scarcely investigated. From the publicly available Gene Expression Omnibus (GEO) datasets, <jats:italic>FHF2<\/jats:italic> (also known as fibroblast growth factor 13, <jats:italic>FGF13<\/jats:italic>) alterations are described in PD patients. <jats:italic>Fgf13<\/jats:italic> gene is significantly decreased in several PD mouse models, and its overexpression alleviates the PD\u2010like pathological phenotype. Although FGF13 is highly expressed in neurons, it functions by preventing glia\u2010dependent inflammatory processes. Mechanistically, FGF13 combines mitochondrial proteins such as MCHT2 (a protein localized on the mitochondrial outer membrane), to anchor mitochondria within the cytoplasm. Under PD\u2010related stress, decreased neuronal FGF13 levels induce the release of the damaged mitochondria, which in turn activate microglia and astrocytes, thereby promoting neurodegeneration. Abacavir, an FDA\u2010applied anti\u2010retroviral drug, is identified to prevent excessive gliosis and neuron loss in both glia\u2010neuron co\u2010cultures and PD mouse models by rejuvenating FGF13 signaling. Collectively, neuronal FGF13 inhibits the transfer of stressed mitochondria to glia, thereby impeding neuroinflammation and neurodegeneration. Abacavir is a promising neuroprotectant and sets a brake to PD progression.<\/jats:p>","DOI":"10.1002\/advs.202503579","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T08:41:45Z","timestamp":1748335305000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Neuronal FGF13 Inhibits Mitochondria\u2010Derived Damage Signals to Prevent Neuroinflammation and Neurodegeneration in a Mouse Model of Parkinson's Disease"],"prefix":"10.1002","volume":"12","author":[{"given":"Nanshan","family":"Song","sequence":"first","affiliation":[{"name":"School of Medicine Nanjing University of Chinese Medicine  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangxu","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neurodegeneration Department of Pharmacology Nanjing Medical University  Nanjing 211166 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