A10 ALS (motor neuron degeneration)

Title

Amyotrophic lateral sclerosis combines two mechanisms already introduced in previous models: aggregation of misfolded proteins (SOD1, TDP-43), with the same nucleation-elongation kinetics used in A03, and glutamatergic excitotoxicity due to failure of the astrocytic transporter EAAT2, analogous to the A05 cascade. Both processes converge in the progressive death of motor neurons, quantified with the same population formalism N used in E14 and A03. The loss of motor neurons reduces the number of functional motor units, partially compensated by collateral reinnervation of surviving axons, until this compensatory mechanism is saturated. Resulting muscle strength and forced vital capacity (FVC), a standard clinical respiratory marker, characteristically decline as the disease progresses.

ID:4292