Heat shock protein beta-8

Heat shock protein beta-8 (HspB8) is a 21.6 kDa molecular chaperone encoded by HSPB8 (UniProt: Q9UJY1). It mediates chaperone-assisted selective autophagy (CASA), a protein quality control mechanism particularly important in mechanically stressed tissues such as muscle. The protein displays temperature-dependent chaperone activity and is involved in maintaining cellular proteostasis.

HspB8 is associated with several neuromuscular disorders including distal hereditary motor neuronopathy type 2 (HMND2), Charcot-Marie-Tooth disease axonal type 2L (CMT2L), and myofibrillar myopathy with rimmed vacuoles (MFM13) (UniProt: Q9UJY1). These monogenic mutations underscore the protein's critical role in neuronal and muscle cell integrity.

In Alzheimer's disease, HspB8 is upregulated in post-mortem AD brain tissue relative to age-matched controls (mean log2 fold-change: 1.00; Chaparral AD proteomics). This elevation was detected across subcellular fractions in TMT-labeled proteomics analysis. The upregulation may reflect a compensatory protein quality control response to the protein aggregation and neuronal stress characteristic of AD pathology.