Rethinking to riluzole mechanism of action: the molecular link among protein kinase CK1δ activity, TDP-43 phosphorylation, and amyotrophic lateral sclerosis pharmacological treatment

[...]over the last years, the incidence and social impact of neurodegenerative diseases have increased, highlighting an urgent need for new and more effective therapeutic strategies to counter these terrible disorders. [...]it has also been demonstrated that riluzole is a highly specific blocker of inactivated Na + channels, which in turn inhibit glutamate release. Riluzole has been shown to increase motor behavior in the rodent, due to a diminished motoneurons loss (Fumagalli et al., 2006). [...]clinical studies have also demonstrated that riluzole slows disease progression in ALS patients (Bensimon et al., 1994). Several pathways have been postulated, ranging from central anti-glutaminergic modulation of excitotoxic pathways, mitochondrial function, and changes to fat metabolism, to peripheral axonal effects on persistent sodium channel function and potentiation of calcium-dependent potassium currents. [...]the uncertainty about its molecular mechanism of action has made slower and complicated the development of more powerful and effective drug candidates.