Role of Mannitol in Modulating the Activity, Structure and Aggregation Propensity of Superoxide Dismutase during Various Neurodegenerative disorders

Abstract

The accumulation of small organic molecules and other low molecular weight metabolites is a widespread response that may protect diverse range of organisms against the environmental stress conditions. Accumulation of high concentrations of these organic metabolites, organisms adapt to the environmental perturbations that maylead to the structural alterations in their cellular proteins. Mannitol is one the main organic osmolyte synthesized in huge amounts as a stress-responsive factor especially in brain cells to retain cellular integrity when cells are exposed to environmental stresses. We intended to investigate the effect of mannitol on functional, structural stability and aggregation pattern of superoxide dismutase, which plays a key role against oxidative stress.We observed that mannitol increased the activity of superoxide dismutase several folds by stabilizing the secondary and tertiary structure of SOD.In addition to this, mannitol inhibited the formation of fibrils. Higher concentrations significantly decreased the formation of high molecular weight oligomers.Thus, Mannitol could be a promising scaffold for the development of therapeutic agentin a variety of neurodegenerative disorders.