Protein aggregation: Consequences, mechanism, characterization and inhibitory strategies

Abstract

Proteins play a major role in the regulation of various cellular functions including the synthesis of structural components. But proteins are stable under physiological conditions only. A slight variation in environmental conditions can cost them huge in terms of conformational stability ultimately leading to aggregation. Under normal conditions, aggregated proteins are degraded or removed from the cell by a quality control system including ubiquitin-proteasomal machinery and autophagy. But they are burdened under diseased conditions or are impaired by the aggregated proteins leading to the generation of toxicity. The misfolding and aggregation of protein such as amyloid-β, α-synuclein, human lysozyme etc., are responsible for certain diseases including Alzheimer, Parkinson, and non- neuropathic systemic amyloidosis respectively. Extensive research has been done to find the therapeutics for such diseases but till now we have got only symptomatic treatment that will reduce the disease severity but will not target the initial formation of nucleus responsible for disease progression and propagation. Hence there is an urgent need to develop the drugs targeting the cause of the disease. For this, a wide knowledge related to misfolding and aggregation under the same heading is required as described in this review alongwith the strategies hypothesized and implemented till now. This will contribute a lot to the work of researchers in the field of neuroscience.

Keywords: Aggregation prone region; Confocal laser scanning microscopy; Preformed fibrils; Protein misfolding; Secondary nucleation; Zetasizer.