Small heat shock protein B8: from cell functions to its involvement in diseases and potential therapeutic applications
Year: 2024
Type: article
Abstract: Heat shock protein family B (small) member 8 (HSPB8) is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock proteins. HSPB8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation, cell division, and migration. HSPB8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective autophagy. In line with this function, the pro-degradative activity of HSPB8 has been found protective in several neurodegenerative and neuromuscular diseases characterized by protein misfolding and aggregation. In cancer, HSPB8 has a dual role being capable of exerting either a pro- or an anti-tumoral activity depending on the pathways and factors expressed by the model of cancer under investigation. Moreover, HSPB8 exerts a protective function in different diseases by modulating the inflammatory response, which characterizes not only neurodegenerative diseases, but also other chronic or acute conditions affecting the nervous system, such as multiple sclerosis and intracerebellar hemorrhage. Of note, HSPB8 modulation may represent a therapeutic approach in other neurological conditions that develop as a secondary consequence of other diseases. This is the case of cognitive impairment related to diabetes mellitus, in which HSPB8 exerts a protective activity by assuring mitochondrial homeostasis. This review aims to summarize the diverse and multiple functions of HSPB8 in different pathological conditions, focusing on the beneficial effects of its modulation. Drug-based and alternative therapeutic approaches targeting HSPB8 and its regulated pathways will be discussed, emphasizing how new strategies for cell and tissue-specific delivery represent an avenue to advance in disease treatments.
Source: Neural Regeneration Research
Institution: University of Milan
Language: English
Topic: Heat shock proteins research
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,500
Funders: Università degli Studi di Milano, Dipartimenti di Eccellenza, Fondazione Telethon, Fondazione Cariplo, Ministero della Salute, Ministero dell’Istruzione, dell’Università e della Ricerca, Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica, Ministero dell'Università e della Ricerca, Agenzia Italiana del Farmaco, Ministero della Salute
Awards: G1253938088, G1666570694, G1741311689, G1947473916, G2117262308, G3103822924, G310635517, THE INTERPLAY BETWEEN THE “RNA/PROTEIN QUALITY CONTROL SYSTEM” AND “EXOSOMES” AS A SPREADING MECHANISM IN AMYOTROPHIC LATERAL SCLEROSIS [EX_ALS], G3175769028, G4645192957, G4737710504, G5204579514, G7547888899, TEAM - Role of TDP-43 self-assembly in health and disEase: molecular characteristics, cellular Aspects and animal Models
OpenAlex ID: W4403619444