Neurodegenerative Multioethiology Lou Gehrig’s Disease – Genetic Mutations, Pharmacological Mechanisms and Applications of Rilusole
Abstract
The most severe motor neuron degenerative illness is Amyotrophic Lateral Sclerosis (ALS, Lou Gehrig's disorder). The aims of the current study are 1) a comparison of genetic and other factors for disease development, 2) an estimation of pharmacological mechanisms of Rilusole for its applications against different diseases; 3) the combinations for the symptomatic treatment of stages ALS progression stages. The investigation has been made through the existing electronical database of medical sources. The most common risk factors for ALS are mutations in genes for SOD1, SETX, FUS, VEGF, VAPB, ANG, TARDBP, FIG4, OPTN, ATXN2, VCP, UBQLN2, SIGMAR1, CHMP2B, PFN1, ERBB4, HNRNPA1, C9orf72, dynactin 1, H46R, A4V. Other risk factors are oxidative stress, glutamate toxicity, autoimmune, protein aggregation, inflammation, and viral infections. Pharmacological effects of Riluzole are a result of the mechanisms of action 1) depression of repetitive firing frequency; 2) suppression of persistent sodium current in motoneurons; 3) potentiation of calcium-dependent potassium current; 4) presynaptic reduction of neurotransmitter release; 5) suppression of postsynaptic neurotransmitter receptor responses. Applied combinations of Riluzole with antioxidants: vitamin E, vitamin C, coenzyme Q10, creatine, and selenium can be used for ALS therapy. For symptomatic therapy nonsteroidal anti-inflammatory drugs are used and opioids for pain and Baclofen and Dantrolene for spasticity. Memantine, Nimesulide, and Gabapentin are considered to be appropriate for further investigations. Due to different mechanisms of action, Riluzole is applied against ALS, Parkinson, Huntington, Machado-Joseph's disease, multiple sclerosis, spinal muscular atrophy, anxiety, autistic, depression, and schizophrenic disorders.
