Glycogen accumulation modulates life span in a mouse model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons in the spinal cord. Using the ALS mouse model expressing the G93A mutant of Superoxide Dismutase 1 (SOD1G93A), we found that glycogen accumulates in the spinal cord during disease progression, and that increased glycogen is associated with reactive astrocytes. Genetic reduction of glycogen levels increases lifespan and alters inflammatory cytokines, while increasing glycogen levels leads to a more rapid disease progression. These results suggest that glycogen in reactive astrocytes contributes to neurotoxicity and disease progression in ALS. Graphical abstract created with BioRender.com. AbstractAmyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons in the spinal cord. Glial cells, including astrocytes and microglia, have been shown to contribute to neurodegeneration in ALS, and metabolic dysfunction plays an important role in the progression of the disease. Glycogen is a soluble polymer of glucose found at low levels in the central nervous system that plays an important role in memory formation, synaptic plasticity, and the prevention of seizures. However, its accumulation in astrocytes and/or neurons is associated with pathological conditions and aging. Importantly, glycogen accumulation has been reported in the spinal cord of human ALS patients and mouse models. I...

Source: Journal of Neurochemistry - July 4, 2023 Category: Neuroscience Authors: M. Kathryn Brewer, Pascual Torres, Vict òria Ayala, Manuel Portero‐Otin, Reinald Pamplona, Pol Andrés‐Benito, Isidro Ferrer, Joan J. Guinovart, Jordi Duran Tags: ORIGINAL ARTICLE Source Type: research