C-Abl Inhibition; A Novel Therapeutic Target for Parkinson's Disease

Title:C-Abl Inhibition; A Novel Therapeutic Target for Parkinson's Disease

Volume: 17 Issue: 1

Author(s): Abdelrahman Ibrahim Abushouk, Ahmed Negida*, Rasha Abdelsalam Elshenawy, Hossam Zein, Ali M. Hammad, Ahmed Menshawy and Wael M.Y. Mohamed

Affiliation:

• Medical Research Group of Egypt, Zagazig, El-Sharkia,Egypt

Keywords: Alzheimer's disease, c-Abelson, nilotinib, Parkinson's disease, tyrosine kinase inhibitors, neurological diseases.

Abstract: Parkinson's disease (PD) is the most prevalent movement disorder in the world. The major pathological hallmarks of PD are death of dopaminergic neurons and the formation of Lewy bodies. At the moment, there is no cure for PD; current treatments are symptomatic. Investigators are searching for neuroprotective agents and disease modifying strategies to slow the progress of neurodegeneration. However, due to lack of data about the main pathological sequence of PD, many drug targets failed to provide neuroprotective effects in human trials. Recent evidence suggests the involvement of C-Abelson (c-Abl) tyrosine kinase enzyme in the pathogenesis of PD. Through parkin inactivation, alpha synuclein aggregation, and impaired autophagy of toxic elements. Experimental studies showed that (1) c-Abl activation is involved in neurodegeneration and (2) c-Abl inhibition shows neuroprotective effects and prevents dopaminergic neuronal' death. Current evidence from experimental studies and the first in-human trial shows that c-Abl inhibition holds the promise for neuroprotection against PD and therefore, justifies the movement towards larger clinical trials. In this review article, we discussed the role of c-Abl in PD pathogenesis and the findings of preclinical experiments and the first in-human trial. In addition, based on lessons from the last decade and current preclinical evidence, we provide recommendations for future research in this area.

Cite this article as:

Abushouk Ibrahim Abdelrahman, Negida Ahmed *, Elshenawy Abdelsalam Rasha , Zein Hossam , Hammad M. Ali , Menshawy Ahmed and Mohamed M.Y. Wael , C-Abl Inhibition; A Novel Therapeutic Target for Parkinson's Disease, CNS & Neurological Disorders - Drug Targets 2018; 17 (1) . https://dx.doi.org/10.2174/1871527316666170602101538