Sequestosome-1 (p62) expression reveals chaperone-assisted selective autophagy in immune-mediated necrotizing myopathies.

Brain Pathology
Norina FischerWerner Stenzel

Abstract

Diffuse myofiber necrosis in the context of inflammatory myopathy is the hallmark of immune-mediated necrotizing myopathy (IMNM). We have previously shown that skeletal muscle fibers of IMNM patients may display nonrimmed vacuoles and sarcoplasmic irregularities. The dysfunctional chaperone activity has been linked to the defective assembly of skeletal muscle proteins and their degradation via lysosomes, autophagy and the proteasomal machinery. This study was undertaken to highlight a chaperone-assisted selective autophagy (CASA) pathway, functionally involved in protein homeostasis, cell stress and the immune response in skeletal muscle of IMNM patients. Skeletal muscle biopsies from 54 IMNM patients were analyzed by immunostaining, as well as by qPCR. Eight biopsies of sIBM patients served as pathological controls, and eight biopsies of nondisease control subjects were included. Alteration of autophagy was detectable in all IMNM biopsy samples highlighted via a diffuse sarcoplasmic staining pattern by p62 and LC3 independent of vacuoles. This pattern was at variance with the coarse focal staining pattern mostly confined to rimmed vacuoles in sIBM. Colocalization of p62 with the chaperone proteins HSP70 and αB-crystalline poin...Continue Reading

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Mar 8, 2020·Neuropathology and Applied Neurobiology·T AyakiR Takahashi
Sep 18, 2020·Current Opinion in Rheumatology·Steven A Greenberg
Aug 28, 2020·Current Opinion in Neurology·Jantima TanboonIchizo Nishino
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