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

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

Journal Name: CNS & Neurological Disorders - Drug Targets

Volume 17 , Issue 1 , 2018

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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.

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

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Article Details

VOLUME: 17
ISSUE: 1
Year: 2018
Page: [14 - 21]
Pages: 8
DOI: 10.2174/1871527316666170602101538

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