DNAJB6 myopathy in an Asian cohort and cytoplasmic/nuclear inclusions

Pathology of frontotemporal dementia with limb girdle muscular dystrophy caused by a DNAJB6 mutation

“…Therefore, this DNAJB6 mutation may be closely related to neurodegeneration. Previously, we reported that DNAJB6 accumulated in the cytoplasm where it co-localized with members of the autophagy complex [4]. In this study, we showed a severe reduction of DNAJB6 staining, and a PRGN and MAPT genes and no abnormal expansion of C9ORF72.…”

Myopathy-causing Mutations in an HSP40 Chaperone Disrupt Processing of Specific Client Conformers

“…Both genetic and sporadic modifications can impair this process, leading to protein misfolding and the formation of protein aggregates that are present in many neuro-and myodegenerative diseases. Molecular chaperones, such as heat shock proteins (HSPs), 3 help combat such aggregation, serving to refold substrates or target them for degradation. Consequently, dysfunction of this protective network of chaperones contributes to a variety of disorders.…”

HSPB8 (heat shock 22kDa protein 8)

“…It enables the ubiquitylation of the mutant superoxide dismutase (mSOD1) protein that is implicated in the development of amyotrophic lateral sclerosis (ALS), promoting its autophagic removal (Crippa et al, 2010a;Crippa et al, 2010b;Rosati et al, 2011;Vos et al, 2011). HspB8/Bag-3 interaction also has an important role in the protection of astrocytes against different protein aggregation diseases, apparently through autophagy-related aggregate clearance (Seidel et al, 2012) and it may contribute to chaperone-assisted selective autophagy in limbgirdle muscular dystrophy type 1D (LGMD1D), a myopathy caused by mutations of the Hsp40 family member DNAJB6 (Sato et al, 2013). During recovery from heat shock, the transcription factor nuclear factor-kappa B (NF-κB) activates selective removal of misfolded or aggregated proteins by controlling the expression of HspB8 and Bag-3 and increasing HspB8/Bag-3 complex formation, thereby increasing cell survival (Nivon et al, 2012).…”

“…Immunohistochemical analysis revealed coaccumulation of HspB8 and members of the chaperone-assisted selective autophagy complex with DNAJB6 in cytoplasmic inclusions (Sato et al, 2013).…”