Genetic Mutations Linked to ALS and other MNDs

In contrast to the slowly progressive ALS phenotype exhibited by the p.V31A mutation, Rosanna Tortelli and other investigators found that a new phenotype in the SOD1 gene, which phenotype represents a very rapid progression and aggressive ALS We reported the discovery of a missense mutation. The study further confirmed the possibility of a strong genotype-phenotype correlation of different SOD1 mutations. Tortelli's research found a heterozygous mutation in exon 4 of the SOD1 gene, resulting in an amino acid substitution from arginine to cysteine ​​at position 115 (p R 115 C).

Specifically, aggregation of TDP - 43, an RNA binding protein, has been found in ALS / MND patients and mutations in the genes encoding these proteins are identified in familial cases of ALS / MND Has been done. These mutations misfold the protein in a prion-like conformation. The misfolded form of TDP - 43 has been found to form cytoplasmic inclusion bodies in diseased neurons and deplete in the nucleus. In addition to ALS / MND and FTLD - U, TDP - 43 pathology is characteristic of many cases of Alzheimer 's disease, Parkinson' s disease and Huntington 's disease. Misfolding of TDP - 43 is primarily guided by its prion - like domain. This domain tends to essentially misfold and pathological mutations in TDP-43 have been found to increase the tendency to misfold, suggesting that these mutations in familial ALS / MND cases The existence of. Like yeast, the prion-like domain of TDP-43 has been shown to be necessary and sufficient for protein misfolding and aggregation.

Scientists have discovered other gene mutations beyond dozens that may be related to amyotrophic lateral sclerosis. These mutations lead to processing changes in RNA molecules (presumably regulatory genes), defects in the protein circulation, defects in the shape and structure of motor neurons, or susceptibility to environmental toxins. Aaron Glatt, Director of Infectious Diseases at Nassau Community Hospital in South Africa, may be genetically similar to ALS and other neurological disorders such as dementia and schizophrenia, but these diseases are different parts of the brain Said that it would affect other areas. The Frontotemporal degeneration Association says that about 30% of ALS patients eventually show signs of frontal regression. This may be similar to FTD. Although FTD does not affect the brain and nervous system controlling body movement, about 10% to 15% of FTD patients develop symptoms of ALS or similar ALS.