骨骼肌
神经炎症
TFEB
生物
中枢神经系统
转基因小鼠
神经科学
转录因子
陶氏病
转基因
细胞生物学
疾病
神经退行性变
内分泌学
炎症
内科学
医学
免疫学
遗传学
基因
作者
Ian Matthews,Allison Birnbaum,Anastasia Gromova,Amy Huang,Kailin Liu,Eleanor A. Liu,Kristen Coutinho,Megan McGraw,Dalton Patterson,Macy T. Banks,Amber C. Nobles,Nam Nguyen,Gennifer E. Merrihew,Lu Wang,Eric Baeuerle,Elízabeth Fernández,Nicolas Musi,Michael J. MacCoss,Helen Cristina Miranda,Albert R. La Spada,Constanza J. Cortés
出处
期刊:Cell Reports
[Elsevier]
日期:2023-11-01
卷期号:42 (11): 113436-113436
被引量:2
标识
DOI:10.1016/j.celrep.2023.113436
摘要
Skeletal muscle has recently arisen as a regulator of central nervous system (CNS) function and aging, secreting bioactive molecules known as myokines with metabolism-modifying functions in targeted tissues, including the CNS. Here, we report the generation of a transgenic mouse with enhanced skeletal muscle lysosomal and mitochondrial function via targeted overexpression of transcription factor E-B (TFEB). We discovered that the resulting geroprotective effects in skeletal muscle reduce neuroinflammation and the accumulation of tau-associated pathological hallmarks in a mouse model of tauopathy. Muscle-specific TFEB overexpression significantly ameliorates proteotoxicity, reduces neuroinflammation, and promotes transcriptional remodeling of the aged CNS, preserving cognition and memory in aged mice. Our results implicate the maintenance of skeletal muscle function throughout aging in direct regulation of CNS health and disease and suggest that skeletal muscle originating factors may act as therapeutic targets against age-associated neurodegenerative disorders.
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