Emerging Targets and Latest Proteomics Based Therapeutic Approaches in Neurodegenerative Diseases

Abstract

Protein homeostasis (proteostasis) is achieved by the interplay among various components and pathways inside a cell. Dysfunction in proteostasis leads to protein misfolding and aggregation which is ubiquitously associated with many neurodegenerative disorders, although the exact role of these aggregate in the pathogenesis remains unknown. Many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and others are characterized by the conversion of specific protein aggregates into protein inclusions and/or plaques in degenerating brains. Apart from the conventional disease specific proteins, such as amyloid-β, α - synuclein, huntingtin protein, and prions that are known to aggregate, a number of other proteins play a vital role in aggravating the disease condition. In this review, we discuss the disease etiology, mechanism, the role of various pathways, molecular machinery including molecular chaperones, protein degradation pathways, and the active formation of inclusions in various neurodegenerative diseases. We also highlight the approaches, strategies, and methods that have been used for the treatment of these complex diseases over the years and the efforts that have potential in the near future.

Keywords: Protein misfolding; aggregation; chaperones; proteosomes; small molecule inhibitors..