IN-SILICO DOCKING STUDIES OF COPPER-ZINC SUPEROXIDE DISMUTASE AND PLANT DERIVATIVES TO IDENTIFY POTENTIAL DRUGS FOR THE TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS

Abstract

Amyotrophic lateral sclerosis (ALS) is a dynamic and lethal disorder caused by degeneration of motor neurons. Most cases of ALS show up sporadically, however around 15-20% of patients have family histories of ALS. It causes muscle weakness and atrophy in entire body due to degeneration of motor neurons. The patients loose all their voluntary muscle functions as the disease progresses but the cognitive and sensory functions remain intact. In spite of the fact that the exact reason for the dominant part of cases is still obscure, mutations in chromosome 21 encoding copper zinc superoxide dismutase ( SOD1 ) has been found in 12-22% of familial cases of the disease. There are evidences that oxidative stress causes death of motor neurons. This enzyme is a powerful antioxidant that protects the cells from damage caused by superoxide, a toxic free radical generated in mitochondria. Free radicals are highly reactive molecules produced by mitochondria during normal metabolism. Free radicals can accumulate and cause damage to DNA and proteins within cells. Till now, over 110 mutations in SOD1 have been linked with ALS disorder. When the defense against oxidative stress fails, programmed cell death (apoptosis) is up-regulated and the motor neurons die. Currently there is only one drug riluzole which is available for the treatment of ALS but it just improves the life of patient by two to three months. We are looking for possible plant derivatives such as alkaloids, terpenoids and flavonoids which may be used as drugs for the cure of ALS.