HSP105

HSP105 is a large heat shock protein that functions as a molecular chaperone, supporting protein folding and maintaining cellular proteostasis under stress conditions^[1][2]. Mechanistically, HSP105 interacts with GRP78 and glycogen synthase kinase-3 (GSK3) to facilitate endoplasmic reticulum (ER) stress-induced caspase-3 activation, thereby promoting apoptosis specifically in ER stress contexts^[1]. In neural systems, HSP105 upregulates hippocampal brain-derived neurotrophic factor (BDNF) levels, enhancing neurogenesis and mitigating depression-like behavior in mouse models^[2]. HSP105 also participates in the Wnt/β-catenin pathway by recruiting protein phosphatase 2A (PP2A) to the β-catenin degradation complex, modulating phosphorylation-dependent β-catenin stability, nuclear translocation, and transcription of target genes^[3]. Overexpression of HSP105 in tumors correlates with elevated nuclear β-catenin and Wnt target gene expression, suggesting a role in cancer progression^[3]. Compared with other HSP isoforms, HSP105 exhibits selective functional interactions in ER stress and Wnt signaling, distinguishing it from stress-inducible HSPs and constitutive HSP70 family members^[1][3]. Small molecule inducers, such as geranylgeranylacetone (GGA), enhance HSP105 expression and its neuroprotective functions, providing potential experimental applications in behavioral and neurodegenerative research^[2]. These findings establish HSP105 as a multifunctional chaperone linking stress responses, cell death, and signal transduction in disease-relevant pathways^[1][3][2].