Heat shock protein beta-1

Heat shock protein beta-1 (HSPB1) is a small molecular chaperone that maintains denatured proteins in a folding-competent state and plays a role in stress resistance and actin organization (UniProt: P04792). It regulates phosphorylation and axonal transport of neurofilament proteins, linking it to neuronal homeostasis.

HSPB1 is associated with peripheral nervous system disorders, including Charcot-Marie-Tooth disease type 2F and hereditary motor neuronopathy type 3 (UniProt: P04792). These monogenic neuropathies involve axonal degeneration and progressive distal muscle weakness, reflecting the protein's critical role in neuronal maintenance.

In Alzheimer's Disease, HSPB1 is significantly upregulated in post-mortem brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of 0.72 across three subcellular fractions. This upregulation may reflect a compensatory cellular response to proteostatic stress and protein misfolding, hallmarks of AD pathology.