Transcriptomic Analysis Reveals the Beneficial Effects of Spermidine in an ALS Mouse Model
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by progressive degeneration of motor neurons and skeletal muscle. Gene expression analysis of the spinal cord and gastrocnemius of the SOD1-G93A ALS mouse model revealed a strong increase in inflammatory pathways and, specifically in the ALS gastrocnemius, a decrease in mitochondrial transcription and an increase in ribosomal protein expression. Treatment of ALS mice with the polyamine spermidine (SPD), a promising molecule in combating neurodegeneration and muscle atrophy, is able to partially restore the expression of more than four thousand genes in gastrocnemius tissue, including the mitochondrial regulator Pgc1α, as well as all the mitochondrial encoded genes and a large class of ribosomal proteins. SPD enhanced mitochondrial bioenergetics, as evidenced by Seahorse experiments, and delayed muscle weakness in vivo, as shown by grip strength records. These findings suggest that SPD can act as a potential supplement in the therapeutic strategy for ALS, offering a foundation for further research to improve patient outcomes.
Authors
- Luciana Mosca (ORCID: https://orcid.org/0000-0003-2748-9021)
- Marianna Nicoletta Rossi (ORCID: https://orcid.org/0000-0003-4485-7738)
- Cristiana Valle (ORCID: https://orcid.org/0000-0002-0914-6511)
- Silvia Scaricamazza (ORCID: https://orcid.org/0000-0002-7177-9459)
- Olga Carletta
- Ermes Filomena
- Manuela Cervelli (ORCID: https://orcid.org/0000-0001-8535-8279)
- Illari Salvatori (ORCID: https://orcid.org/0000-0002-8397-8500)
- Roberto Mattioli (ORCID: https://orcid.org/0000-0002-4452-9753)
- Cristian Fiorucci (ORCID: https://orcid.org/0000-0001-5804-3909)
- Davide Laurenti (ORCID: https://orcid.org/0009-0008-1148-5898)
- Anna Maria D'Erchia
- Alberto Ferri
- Rachele Di Santo (ORCID: https://orcid.org/0009-0005-2002-3431)
Institutions
- Roma Tre University (IT)
- Foro Italico University of Rome (IT)
- Istituto di Farmacologia Traslazionale (IT)
- National Cancer Institute (MY)
- Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IT)
- Fondazione Santa Lucia (IT)
- National Research Council (IT)
- National Cancer Research Institute (GB)
- University of Bari Aldo Moro (IT)
- Sapienza University of Rome (IT)
Publication Details
- Journal
- Biomolecules
- Published
- 2026-04-10
- DOI
- https://doi.org/10.3390/biom16040566
- Primary Topic
- Amyotrophic Lateral Sclerosis Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Regione Puglia