Amyotrophic lateral sclerosis (ALS), also called Lou Gehrig’s disease, is a late-onset progressive motor neuron disease first identified in 1869 by Jean-Martin Charcot. Its incidence is approximately two cases per 100,000, with a slightly higher prevalence in men. The progressive degeneration of motor neurons in ALS leads to neuron death and loss of muscle function. Patients become partially or totally paralyzed, but their cognitive functions usually remain unaffected. There is no cure for ALS and the disease is usually fatal within three to five years of the onset of symptoms. About 90% of ALS cases are sporadic, while approximately 10% are inherited in a dominant manner. Mutations in the gene coding for superoxide dismutase 1 (SOD1) account for 20% of all familial cases. To date, more than 140 mutations have been found in the SOD1 gene, and transgenic mice overexpressing various SOD1 mutants develop an ALS-like phenotype through a gain of unknown toxic properties.

Intermediate Filament Alterations in Amyotrophic Lateral Sclerosis
The neuronal cytoskeleton is composed of three interconnected structures: actin microfilaments, microtubules, and intermediate filaments (IFs). Neurofilaments (NFs) are the major IFs present in adult neurons and their expression is restricted to neuronal cell types. Neurons express differentially several IF proteins depending on their stage of development or their localization in the nervous system: nestin (200kDa), NF triplet proteins (NFL [light, 68kDa], NFM [medium, 160kDa], and NFH [heavy, 205kDa]), α-internexin (66kDa), peripherin (57kDa), and synemin (41kDa).¹

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