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

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 divis...

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Main Authors: 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
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2025-10-01
Series:Neural Regeneration Research
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Online Access:https://journals.lww.com/10.4103/NRR.NRR-D-24-00517
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author 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
author_facet 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
author_sort Marta Chierichetti
collection DOAJ
description 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.
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spelling doaj-art-f1af290d3ec0401ca04aaa8e1c7985582024-12-09T09:33:31ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53741876-79582025-10-0120102872288610.4103/NRR.NRR-D-24-00517Small heat shock protein B8: from cell functions to its involvement in diseases and potential therapeutic applicationsMarta ChierichettiRiccardo CristofaniValeria CrippaVeronica FerrariMarta CozziElena CasarottoPaola PramaggioreLaura CornaggiaGuglielmo PatelliAli MohamedMargherita PiccolellaMariarita GalbiatiPaola RusminiBarbara TedescoAngelo PolettiHeat 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.https://journals.lww.com/10.4103/NRR.NRR-D-24-00517aggregationautophagycancerchaperonechaperone-assisted selective autophagycognitive impairmenthspb8neuroinflammationneuromuscular diseasestherapy
spellingShingle 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
Small heat shock protein B8: from cell functions to its involvement in diseases and potential therapeutic applications
Neural Regeneration Research
aggregation
autophagy
cancer
chaperone
chaperone-assisted selective autophagy
cognitive impairment
hspb8
neuroinflammation
neuromuscular diseases
therapy
title Small heat shock protein B8: from cell functions to its involvement in diseases and potential therapeutic applications
title_full Small heat shock protein B8: from cell functions to its involvement in diseases and potential therapeutic applications
title_fullStr Small heat shock protein B8: from cell functions to its involvement in diseases and potential therapeutic applications
title_full_unstemmed Small heat shock protein B8: from cell functions to its involvement in diseases and potential therapeutic applications
title_short Small heat shock protein B8: from cell functions to its involvement in diseases and potential therapeutic applications
title_sort small heat shock protein b8 from cell functions to its involvement in diseases and potential therapeutic applications
topic aggregation
autophagy
cancer
chaperone
chaperone-assisted selective autophagy
cognitive impairment
hspb8
neuroinflammation
neuromuscular diseases
therapy
url https://journals.lww.com/10.4103/NRR.NRR-D-24-00517
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