Genetic approach in amyotrophic lateral sclerosis

Area of Science:

• Genetics
• Neuroscience
• Biochemistry

Background:

• Amyotrophic lateral sclerosis type 1 (ALS1) is primarily associated with mutations in the superoxide dismutase type 1 (SOD1) gene.
• The SOD1 gene encodes an enzyme crucial for protecting cells against oxygen-derived free radical damage.
• Pathophysiological mechanisms in ALS1 involve ischemia, but emerging evidence points to broader causes.

Purpose of the Study:

• To review the genetic landscape of ALS1, focusing on SOD1 mutations.
• To explore the genetic heterogeneity and etiological diversity of both familial and sporadic ALS1.
• To highlight the scarcity of molecular genetics studies in Mexico and mention clinical findings.

Main Methods:

• Review of molecular studies on SOD1 gene mutations in ALS1.
• Analysis of common point mutations in familial ALS1 (p.A4V, p.I113Y, p.G37R, p.D90A, p.E100G).
• Consideration of intronic mutations and genes involved in sporadic ALS1 (SETX, C9orf72).

Main Results:

• Point mutations in SOD1 are the most frequent cause of familial ALS1, with specific mutations accounting for over 80% of cases.
• Genetic heterogeneity is evident, with different genes implicated in sporadic ALS1.
• Molecular and pathogenic mechanisms are diverse, extending beyond oxidative stress and ischemia.

Conclusions:

• ALS1 is a genetically heterogeneous disease with varied etiologies for familial and sporadic forms.
• Understanding the molecular basis of ALS1 requires considering multiple genes and pathogenic pathways.
• Further molecular genetics research in regions like Mexico is needed, alongside investigating clinical markers like adipsin.