Amyotrophic lateral sclerosis

or Charcot's disease
Amyotrophic lateral sclerosis (ALS) or Charcot's disease is a neurodegenerative disease characterized by progressive muscular paralysis. It is due to the degeneration of neurons of voluntary motricity that are located in the frontal cortex, the brain stem and the spinal cord. ALS is a relatively rare disease with a prevalence of 1/20 000. In about 10% of cases, it is a hereditary disease. The most common genetic mutations in Europe are those affecting the genes C9ORF72, SOD-1, TARDBP, FUS.

Joint developments in genetics and tissue analysis methods by immunohistochemistry have shown that the disease was related to abnormal protein deposition in the central nervous system.
In most cases of ALS, the TDP43 protein, normally contained in the nucleus of neurons, accumulates in the cytoplasm. The same protein is identified in frontotemporal lobar degeneration (LFT) lesions suggesting mechanisms common to both diseases.
In hereditary SLAs, the accumulated protein is not always TDP43 but can be the one produced by the mutated gene: for example the SOD-1 protein in mutations of the SOD-1 gene, the FUS protein in gene mutations FUS. TDP-43 and FUS are RNA binding proteins, which regulate different stages of RNA metabolism. The mechanisms by which accumulated proteins are toxic to the nervous system are not yet fully known.

Anterior horn of the spinal cord: H&Ex400.

Corne antérieure de la moelle HEx40
Corne antérieure de la moelle TDP43x400

Anterior horn of the spinal cord: TDP43x400.

Anterior horn of the spinal cord: Bunina bodies (Cystatine C x400).

Corne antérieure de la moelle, corps de bunina (Cystatine C + x400).