Cortical Hyperexcitability in the Driver’s Seat in ALS

Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by the degeneration of cortical and spinal motor neurons. With no effective treatment available to date, patients face progressive paralysis eventually succumb due respiratory failure within only few years. Recent research has revealed multifaceted nature mechanisms cell types involved in neuron degeneration, thereby opening up new therapeutic avenues. Intriguingly, two key features present both ALS rodent models are hyperexcitability hyperconnectivity, which still not fully understood. We here recapitulate current findings arguing for autonomous non-cell causing excitation inhibition imbalance, neurons ALS. Moreover, we will highlight recent evidence that strongly indicates cardinal role cortex as main driver source disease, thus corticofugal trajectory pathology.