Final answer:
The metabolic basis for ALS involves the degeneration of motor neurons due to calcium dysregulation, genetic factors like mutations in the SOD1 gene, environmental factors, and altered GluA2 mRNA expression affecting AMPA receptors.
Step-by-step explanation:
The metabolic basis for Amyotrophic lateral sclerosis (ALS, also called Lou Gehrig's Disease) is primarily linked to the degeneration of motor neurons that control voluntary movements. Calcium dysregulation is a central aspect in this degeneration. Peculiar to ALS is that motor neurons in the spinal cord, brain stem, and motor cortex progressively degenerate, leading to muscle atrophy, paralysis, and eventually death, with patients fully aware of their condition due to the lack of cognitive deficit.
Genetically, about 20% of familial ALS cases are linked to mutations in the SOD1 gene, which encodes a copper/zinc-dependent superoxide dismutase protein, with other mutations identified through genome-wide association studies. Although sporadic ALS lacks specific target mutations, some environmental factors have been implicated in ALS-like neurodegeneration. A common characteristic of familial ALS and experimental mouse models is the involvement of mutant SOD1.
Furthermore, research has indicated the altered expression of GluA2 mRNA in motor neurons of ALS patients, suggesting that AMPA receptors, which when dysregulated can permit harmful levels of calcium into cells, play a role in the disease. Therefore, pharmacological antagonism of these receptors might slow ALS progression.