C-Abl inhibition; a novel therapeutic target for Parkinson’s disease
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 neu...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English English English |
| Published: |
Bentham Science Publishers B.V.
2018
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| Subjects: | |
| Online Access: | http://irep.iium.edu.my/58689/ http://irep.iium.edu.my/58689/ http://irep.iium.edu.my/58689/ http://irep.iium.edu.my/58689/1/58689_C-Abl%20inhibition.pdf http://irep.iium.edu.my/58689/2/58689_C-Abl%20inhibition_SCOPUS.pdf http://irep.iium.edu.my/58689/3/58689_C-Abl%20inhibition_WOS.pdf |
| Summary: | 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 PD. However,
recently, due to the ignorance of the main pathological sequence of PD, many drug targets failed to
provide neuroprotective effects in human trials. Currently, a huge amount of evidence suggests the involvement
of C-Abelson (c-Abl) tyrosine kinase enzyme in the pathology of PD. C-abl plays a role in
PD pathology on the levels of parkin activation, alpha synuclein aggregation, and impaired autophagy
of toxic elements. Experimental studies showed that (1) c-abl activation is involved in neuronal death
and (2) c-abl inhibition shows neuroprotective effects and prevents dopaminergic neurons’ 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 pathology and the findings of preclinical
experiments and the first in-human trial. In addition, based on the lessons of the last decade
and current preclinical evidence, we provide recommendations for future research in this area. |
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