Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (10): 2872-2886.doi: 10.4103/NRR.NRR-D-24-00517

Previous Articles     Next Articles

Small heat shock protein B8: from cell functions to its involvement in diseases and potential therapeutic applications

Marta Chierichetti, Riccardo Cristofani, Valeria Crippa, Veronica Ferrari, Marta Cozzi, Elena Casarotto, Paola Pramaggiore, Laura Cornaggia, Guglielmo Patelli, Ali Mohamed, Margherita Piccolella, Mariarita Galbiati, Paola Rusmini, Barbara Tedesco*, #, Angelo Poletti*, #   

  1. Laboratory of Experimental Biology, Dipartimento di Scienze Farmacologiche e Biomolecolari “Rodolfo Paoletti” (DiSFeB), Università degli Studi di Milano, Milan, Italy
  • Online:2025-10-15 Published:2025-02-07
  • Contact: Barbara Tedesco, PhD, barbara.tedesco@unimi.it; Angelo Poletti, PhD, angelo.poletti@unimi.it.
  • Supported by:
    This work was supported by: Fondazione Telethon - Italy (No. GGP19128 to AP); Fondazione Cariplo - Italy (No. 2021-1544 to RC); Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica (AriSLA) - Italy (No. MLOpathy to AP; Target-RAN to AP); Association Française contre les Myopathies - France (AFM Telethon No. 23236 to AP); Kennedy’s Disease Association - USA (2018 grant to RC; 2020 grant to MG); Ministero dell’Università e della Ricerca (MIUR) – Italy (PRIN—Progetti di ricerca di interesse nazionale (No. 2017F2A2C5 to AP; No. 2022EFLFL8 to AP; No. 2020PBS5MJ to VC; No. 2022KSJZF5 to VC); PRIN – Progetti di ricerca di interesse nazionale - bando 2022, PNRR finanziato dall’Unione europea – Next Generation EU, componente M4C2, investimento 1.1 (No. P2022B5J32 to RC and No. P20225R4Y5 to VC); CN3: RNA – Codice Proposta: CN_00000041; Tematica Sviluppo di terapia genica e farmaci con tecnologia a RNA (Centro Nazionale di Ricerca – CN3 National Center for Gene Therapy and Drugs based on RNA Technology to AP); Progetto Dipartimenti di Eccellenza (to DiSFeB); Ministero della Salute, Agenzia Italiana del Farmaco (AIFA) – Italy (Co_ALS to AP); Università degli Studi di Milano (piano di sviluppo della ricerca (PSR) UNIMI —linea B (to RC and BT).

PDF

116

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 chaperoneassisted 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.

Key words: aggregation,  , autophagy,  , cancer,  , chaperone,  , chaperone-assisted selective autophagy,  , cognitive impairment,  , HSPB8,  , neuroinflammation,  , neuromuscular diseases,  , therapy