PXD045241

PXD045241 is an original dataset announced via ProteomeXchange.

Title	Skeletal Muscle TFEB Signaling Promotes Central Nervous System Function and Reduces Neuroinflammation during Aging and Neurodegenerative Disease
Description	Skeletal muscle has recently arisen as a novel 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 novel transgenic mouse with enhanced skeletal muscle lysosomal and mitochondrial function via targeted overexpression of Transcription Factor E-B (TFEB). We have discovered that the resulting geroprotective benefits in skeletal muscle reduces neuroinflammation and accumulation of tau-associated pathological hallmarks in a mouse model of tau pathology. Muscle TFEB overexpression also significantly ameliorates proteotoxicity, reduces neuroinflammation and promotes transcriptional remodeling of the aging CNS, preserving cognition and memory in aging mice. Our results implicate the maintenance of skeletal muscle function throughout aging to direct regulation of CNS health and disease, and suggest that skeletal-muscle originating factors may act as novel therapeutic targets against age-associated neurodegenerative disorders.
HostingRepository	PanoramaPublic
AnnounceDate	2023-12-06
AnnouncementXML	Submission_2023-12-06_10:03:22.833.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Gennifer Merrihew
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	Carbamidomethyl
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-09 09:48:08	ID requested
⏵ 1	2023-12-06 10:03:24	announced

Matthews I, Birnbaum A, Gromova A, Huang AW, Liu K, Liu EA, Coutinho K, McGraw M, Patterson DC, Banks MT, Nobles AC, Nguyen N, Merrihew GE, Wang L, Baeuerle E, Fernandez E, Musi N, MacCoss MJ, Miranda HC, La Spada AR, Cortes CJ, Skeletal muscle TFEB signaling promotes central nervous system function and reduces neuroinflammation during aging and neurodegenerative disease. Cell Rep, 42(11):113436(2023) [pubmed]

submitter keyword: DIA, skeletal muscle, transcription factor, aging, neurodegenerative disease

Michael MacCoss
contact affiliation	University of Washington
contact email	maccoss@uw.edu
lab head
Gennifer Merrihew
contact affiliation	University of Washington
contact email	genn@uw.edu
dataset submitter

Panorama Public dataset URI