{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T17:31:36Z","timestamp":1792949496430,"version":"4.5.0"},"reference-count":82,"publisher":"American Society for Clinical Investigation","issue":"14","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":76,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R01 NS119873"],"award-info":[{"award-number":["R01 NS119873"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["R01 AG076154"],"award-info":[{"award-number":["R01 AG076154"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["T32 GM145470,T32 GM007863"],"award-info":[{"award-number":["T32 GM145470,T32 GM007863"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,22]]},"abstract":"<jats:p>\n                    Skeletal muscle pathology is a critical but poorly understood contributor to neuromuscular degeneration in spinal and bulbar muscular atrophy (SBMA), a CAG\/polyglutamine (polyQ) expansion disorder caused by mutation in the androgen receptor (AR). Using a gene-targeted SBMA mouse model, we applied single-nucleus RNA sequencing to identify a disease-specific population of skeletal muscle myonuclei that replaced normal myonuclear subtypes. This transition was associated with dysregulation of the pathway governed by PGC-1\u03b1, a central regulator of myofiber specification and metabolic identity. PGC-1\u03b1 dysfunction in SBMA muscle was age, hormone, and polyQ length dependent and was partially rescued by subcutaneous delivery of\n                    <jats:italic>AR<\/jats:italic>\n                    -targeted antisense oligonucleotides. Integrated ChIP-seq and RNA-seq analyses revealed that aberrant PGC-1\u03b1 activity promoted the expression of a distinct set of myofiber specification genes while downregulating those that define healthy Type IIb and Type IIx myonuclei. We propose a model in which this dysfunction arose downstream of polyQ-mediated sequestration of PGC-1\u03b1 cofactors MEF2, CREB, and CBP, leading to transcriptional reprogramming and cellular dysfunction. These findings implicated PGC-1\u03b1 dysregulation as a key event linking AR polyQ expansion to skeletal muscle degeneration and suggested a shared mechanism for polyQ-mediated muscle pathology across related neurodegenerative diseases.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.203215","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T16:00:24Z","timestamp":1778169624000},"source":"Crossref","is-referenced-by-count":1,"title":["PGC-1\u03b1 pathway dysregulation disrupts myofiber specification in a mouse model of SBMA"],"prefix":"10.1172","volume":"11","author":[{"given":"Curtis J.","family":"Kuo","sequence":"first","affiliation":[{"name":"Department of Pathology,"},{"name":"Cellular and Molecular Biology Graduate Program, Medical Scientist Training Program,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura B.","family":"Chopp","sequence":"additional","affiliation":[{"name":"University of Michigan Medical School, 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