Loss of C9orf72 impacts the peripheral neuromuscular system via immune dysregulation and accelerates the progression of amyotrophic lateral sclerosis in SOD-1 mutant mice
Our findings underscore the critical role of C9orf72 in maintaining neuromuscular health through its influence on myelination, immune response regulation, and NMJ integrity. Loss of C9orf72 function exacerbates ALS progression by promoting SC dysfunction and immune dysregulation. This highlights the significance of preserving normal C9orf72 function in ALS therapies through antisense oligonucleotides strategies. Furthermore, targeting immune responses and myelination pathways may offer novel avenues for ALS treatment strategies.
Authors
- Valentina Bonetto
- Angelo Quattrini (ORCID: https://orcid.org/0000-0002-8226-8320)
- Francesca Sironi (ORCID: https://orcid.org/0000-0001-5287-3784)
- Mami Kurosaki (ORCID: https://orcid.org/0000-0001-8231-713X)
- Mattia Freschi (ORCID: https://orcid.org/0000-0003-0800-5087)
- Massimo Tortarolo (ORCID: https://orcid.org/0000-0003-3078-2341)
- Paola Podini (ORCID: https://orcid.org/0000-0002-4757-9887)
- Francesco Gentile (ORCID: https://orcid.org/0000-0002-1847-5608)
- Caterina Bendotti (ORCID: https://orcid.org/0000-0003-1055-1271)
- Mineko Terao (ORCID: https://orcid.org/0000-0002-9976-9869)
- Sonia Mazzucchi (ORCID: https://orcid.org/0000-0001-7027-1218)
- Paola Parlanti (ORCID: https://orcid.org/0000-0002-2163-1296)
- Laura Camporeale (ORCID: https://orcid.org/0009-0002-6984-2823)
- Nilo Riva (ORCID: https://orcid.org/0000-0002-0513-9517)
- Valentina Cappello (ORCID: https://orcid.org/0000-0002-2385-8320)
- Giulio Federico Giovanetti
- Eliana Arcadipane
Institutions
- Piaggio (Italy) (IT)
- Vita-Salute San Raffaele University (IT)
- Mario Negri Institute for Pharmacological Research (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT)
Publication Details
- Journal
- Journal of Neuroinflammation
- Published
- 2025-11-15
- DOI
- https://doi.org/10.1186/s12974-025-03597-y
- Primary Topic
- Amyotrophic Lateral Sclerosis Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00