Nanozyme mediated SOD1 strategy linked to nanochaperone facilitate aggregation inhibition in amyotrophic lateral sclerosis.

Abstract

Unlike natural enzymes, nanomaterial based ‘nanozyme’ offers higher stability and easy storage to address a steady function even in the extreme conditions of pH, temperature and molecular resistance to digestion from proteases. Nanozyme scavenging surplus reactive oxygen species (ROS) can serve as an effective tool to treat various neurodegenerative diseases. Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the loss of the upper motor neuron and lower motor neuron leading to destruction of motor neurons and extra motor symptoms. Thus, loss/inefficiency of SOD1 enzymatic activity and its aggregation, both are known to be associated with ALS disease pathology. Here, nanoparticle (NP) functionalization strategy is used to develop a histidine (His) based superoxide dismutase-I (SOD1) therapeutic substitute with a dual role of nanozyme and nanochaperone activity. Zinc and Copper are an essential micronutrient of biological milieu in humans and act as an integral part of several enzymes active sites. His-functionalized nanozyme was found significant for scavenging excess ROS and targeting mitochondria with cytoprotective effect in the ALS model in-vitro. The nanochaperone role was characterized by its ability to reduce the aggregation of human apoSOD1WT and apoSOD1G93A mutant. In particular, a critical analysis of Amide I and III Raman band, specified to protein secondary structural elements suggested the decrease of a-helix and the early predominant b-sheets in human SOD1 in the absence of nanochaperone. But a reverse phenomenon was observed in the presence of nanochaperons. The dual role of nanozyme-nanochaperone provides a promising insightful into ALS pathology and may open new avenues for future therapeutics.