2. Academic Validation
  3. Polyamine metabolism dysregulation contributes to muscle fiber vulnerability in ALS

Polyamine metabolism dysregulation contributes to muscle fiber vulnerability in ALS

  • Cell Rep. 2025 Jan 28;44(1):115123. doi: 10.1016/j.celrep.2024.115123.
Veronica Ruggieri 1,  Silvia Scaricamazza 2,  Andrea Bracaglia 1,  Chiara D'Ercole 3,  Cristina Parisi 1,  Paolo D'Angelo 1,  Daisy Proietti 4,  Chiara Cappelletti 5,  Alberto Macone 5,  Biliana Lozanoska-Ochser 6,  Marina Bouchè 7,  Lucia Latella 8,  Cristiana Valle 2,  Alberto Ferri 2,  Lorenzo Giordani 9,  Luca Madaro 10
Affiliations

Affiliations

  • 1 Department of Anatomical, Histological, Forensic Sciences and Orthopedics, Sapienza University of Rome, 00161 Rome, Italy; Laboratory affiliated with Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy.
  • 2 Laboratories of Neurochemistry and of Molecular and Cellular Neurobiology, IRCCS, Fondazione Santa Lucia, 00143 Rome, Italy; National Research Council (CNR), Institute of Translational Pharmacology (IFT), 00133 Rome, Italy.
  • 3 Department of Anatomical, Histological, Forensic Sciences and Orthopedics, Sapienza University of Rome, 00161 Rome, Italy; Sorbonne Université, INSERM UMRS 974, Association Institut de Myologie, Centre de Recherche en Myologie, 75013 Paris, France.
  • 4 Cell Therapy for Myopathies Unit, Division of Neurosciences, San Raffaele Hospital, 20132 Milano, Italy.
  • 5 Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy.
  • 6 Department of Medicine & Surgery LUM University, 70010 Casamassima, Italy.
  • 7 Department of Anatomical, Histological, Forensic Sciences and Orthopedics, Sapienza University of Rome, 00161 Rome, Italy.
  • 8 National Research Council (CNR), Institute of Translational Pharmacology (IFT), 00133 Rome, Italy.
  • 9 Sorbonne Université, INSERM UMRS 974, Association Institut de Myologie, Centre de Recherche en Myologie, 75013 Paris, France. Electronic address: lorenzo.giordani@sorbonne-universite.fr.
  • 10 Department of Anatomical, Histological, Forensic Sciences and Orthopedics, Sapienza University of Rome, 00161 Rome, Italy; Laboratory affiliated with Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy. Electronic address: luca.madaro@uniroma1.it.
PMID: 39932195 DOI: 10.1016/j.celrep.2024.115123
Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease causing progressive paralysis due to motor neuron degeneration with no curative therapy despite extensive biomedical research. One of the primary targets of ALS is skeletal muscle, which undergoes profound functional changes as the disease progresses. To better understand how altered innervation interferes with muscle homeostasis during disease progression, we generated a spatial transcriptomics dataset of skeletal muscle in the SOD1G93A mouse model of ALS. Using this strategy, we identified polyamine metabolism as one of the main altered pathways in affected muscle fibers. By establishing a correlation between the vulnerability of muscle fibers and the dysregulation of this metabolic pathway, we show that disrupting polyamine homeostasis causes impairments similar to those seen in ALS muscle. Finally, we show that restoration of polyamine homeostasis rescues the muscle phenotype in SOD1G93A mice, opening new perspectives for the treatment of ALS.

Keywords

CP: Metabolism; CP: Neuroscience; amyotrophic lateral sclerosis; muscular atrophy; neuromuscular junction; polyamines; skeletal muscle; spatial transcriptomics.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z