Expression and role of HSPA5 in environmental toxin-induced neurological disorders

HSPA5 is a member of the HSP70 family of heat shock proteins (HSPs) and functions as a chaperone protein within the endoplasmic reticulum (ER). It plays a role in maintaining ER homeostasis, assists in correct protein folding, and triggers the unfolded protein response. Environmental toxins-such as heavy metals, microplastics (MPs), and air pollutants-can cause cellular damage. These toxins can trigger ER stress, resulting in the buildup of proteins that are misfolded or not properly folded, which in turn upregulates HSPA5 expression. Moderate activation of HSPA5 serves as a protective mechanism aimed at restoring protein homeostasis and promoting cell survival; however, sustained and severe ER stress may cause HSPA5 to malfunction, ultimately leading to the activation of the apoptotic pathway and resulting in cell death. Furthermore, HSPA5-mediated mechanisms are closely associated with the prodromal initiation and subsequent escalation of neurodegenerative syndromes. This article focuses on the role of HSPA5 in environmental toxin-induced neurotoxicity and neurodegenerative diseases, with the aim of investigating changes in HSPA5 expression and its regulatory functions in neurotoxicity, thereby providing new strategies for the study of environment-related neurodegenerative diseases.