Excitotoxicity in amyotrophic lateral sclerosis: a key pathogenic mechanism - PubMed
4 hours ago
- #ALS pathogenesis
- #glutamate excitotoxicity
- #neurodegenerative disease
- Excitotoxicity is a key pathogenic mechanism in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting motor neurons.
- ALS involves multiple factors, including oxidative stress, inflammation, glutamate excitotoxicity, mitochondrial dysfunction, protein aggregation, and apoptosis.
- Genetic mutations (e.g., SOD1, C9ORF72) contribute to protein misfolding and aggregation, disrupting glutamate homeostasis and leading to calcium-mediated neurotoxicity.
- Oxidative stress impairs calcium regulation and organelle function in motor neurons, while dysregulated glutamate signaling reduces astrocytic clearance, worsening excitotoxicity.
- A vicious cycle of reactive oxygen species production exacerbates glutamate imbalance, increasing neuronal damage and glial dysfunction.
- Current treatments and clinical trials aim to reduce excitotoxicity, but there is a need for novel, targeted therapies to slow ALS progression.