Identification and Characterization of Cathepsins in Parkinsonism.

Abstract

Parkinson’s is the most chronic brain and hypokinetic movement disorder mostly characterized by the progressive neurodegeneration in dopaminergic neurons of substantia nigra region in brain. Many therapies, medications, surgeries, and drug-based treatment approaches have shown symptomatic improvements in Parkinson’s patients, but this threatening neurodegenerative disorder has no reliable treatment till date. These treatment strategies do not halt the progressive nature of this chronic disorder but their long-term use result in adverse side effects. Despite the rapid advancement in experimental and clinical research on Parkinson’s Disease the underlying mechanisms and pathological pathways remains unknown. The uncontrolled apoptosis results in formation and deposition of protein(alpha-synuclein) aggregates and these are the neuropathological hall marks of Parkinson’s disease. Genetic and environmental factors proved to be potential causes. Cathepsin are lysosomal proteases that offer potential therapeutic target in developing treatment for Parkinson’s disease. The differential expression of cathepsin in pathological condition can be taken as an advantage in designing cathepsin based diagnostic markers and therapeutic targets. The use of selective cathepsin inhibitors is emerging as a safe therapeutic approach. The recent advancement in the proteomic-based approaches can be used for the identification of novel proteins and offers opportunity to get better understanding of the mechanism of action of cathepsins. These observations set a platform for future investigations in designing a better and selective cathepsin inhibitors. The cathepsin D protein appear to be a promising compound that could be used for future development of drugs targeting neurodegenerative disorders. Our results imply CTSD as a major lysosomal function regulator and potential entity in degrading the misfolded protein aggregates. Findings of this study implicate that increasing the level and activity of CATD could provide promising and better treatment strategies for maintaining lysosomal functions and in prevention and treatment of neurodegenerative diseases