Cellular and molecular mechanisms of motor neuron death in amyotrophic lateral sclerosisRicardo Tapia Amyotrophic lateral sclerosis (ALS), which was described since 1869 by Jean Martin Charcot, is a devastating neurodegenerative disease characterized by the selective and progressive loss of upper and lower motor neurons of the cerebral cortex, brainstem and the spinal cord. The cognitive process is not affected and is not merely the result of aging because may occur at young ages. The only known cause of the disease is associated with genetic mutations, mainly in the gene encoding superoxide dismutase 1 (familial ALS), whereas there is no known cause of the sporadic form of ALS (SALS), which comprises >90% of cases. Both ALS types develop similar histopathological and clinical characteristics, and there is no treatment or prevention of the disease. Because effective treatments for ALS, as for other neurodegenerative diseases, can only result from the knowledge of their cellular and molecular pathophysiological mechanisms, research on such mechanisms is essential. Although progress in neurochemical, physiological and clinical investigations in the last decades has identified several mechanisms that seem to be involved in the cell death process, such as glutamate-mediated excitotoxicity, alterations of inhibitory circuits, inflammatory events, axonal transport deficits, oxidative stress, mitochondrial dysfunction and energy failure, the understanding of the origin and temporal progress of the disease is still incomplete and insufficient. |
Contents
a perspective | 5 |
Investigating cell death mechanisms in amyotrophic lateral sclerosis using transcriptomics | 8 |
Differential autophagy power in the spinal cord and muscle of transgenic ALS mice | 18 |
Early gene expression changes in spinal cord from SOD1G93A Amyotrophic Lateral Sclerosis animal model | 30 |
Mitochondrial DNMT3A and DNA methylation in skeletal muscle and CNS of transgenic mouse models of ALS | 47 |
Astrocytes expressing mutant SOD1 and TDP43 trigger motoneuron death that is mediated via sodium channels and nitroxidative stress | 63 |
Phenotypic transition of microglia into astrocytelike cells associated with disease onset in a model of inherited ALS | 78 |
Beta2 microglobulin is important for disease progression in a murine model for amyotrophic lateral sclerosis | 86 |
An emerging role for misfolded wildtype SOD1 in sporadic ALS pathogenesis | 110 |
A seeded propagation of Cu Znsuperoxide dismutase aggregates in amyotrophic lateral sclerosis | 126 |
Differential effects on KCC2 expression and spasticity of ALS and traumatic injuries to motoneurons | 131 |
Gacyclidine improves the survival and reduces motor deficits in a mouse model of amyotrophic lateral sclerosis | 142 |
implications for ALS therapy | 151 |
Cellular and molecular mechanisms involved in the neuroprotective effects of vegf on motoneurons | 158 |
Histone deacetylases and their role in motor neuron degeneration | 165 |
energy signaling and structure | 172 |
Neuroimmunity dynamics and the development of therapeutic strategies for amyotrophic lateral sclerosis | 91 |
Redox environment is an intracellular factor to operate distinct pathways for aggregation of cuznsuperoxide dismutase in amyotrophic lateral sclerosis | 101 |
Bloodcns barrier impairment in als patients versus an animal model | 182 |