Hypothesis-free evaluation of circulating metabolome provides cell-specific insights regarding the role of energy substrate availability in amyotrophic lateral sclerosis - PubMed
5 days ago
- #Metabolomics
- #Energy metabolism
- #Amyotrophic lateral sclerosis
- Hypothesis-free Mendelian randomization analysis identified five metabolites causally linked to ALS risk.
- Higher serum glycoprotein acetyls and peptide DSGEGDFXAEGGGVR increase ALS risk, while phenylalanylserine, isobutyrylcarnitine, and acetylcarnitine are protective.
- DSGEGDFXAEGGGVR is linked to glucose metabolism and neuronal glucose uptake via GLUT3, influencing ALS risk.
- Elevated acetylcarnitine and lactate levels in ALS patients correlate with delayed symptom onset and longer survival.
- Increased plasma fructose is associated with shorter survival time in ALS patients.
- Neurons and astrocytes with ALS-associated C9orf72 mutations show reduced metabolic flexibility.
- The study suggests impaired energy substrate availability contributes to ALS risk and severity.
- Findings support investigating metabolic interventions for ALS treatment or prevention.