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...

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Main Authors:	Abushouk, Abdelrahman Ibrahim, Negida, Ahmed, Abdelsalam Elshenawy, Rasha A, Zein, Hossam, Hammad, Ali M, Menshawy, Ahmed, Mohamed, Wael Mohamed Yousef
Format:	Article
Language:	English English English
Published:	Bentham Science Publishers B.V. 2018
Subjects:	R Medicine (General)
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

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recordtype	eprints
spelling	iium-586892018-06-26T09:02:09Z http://irep.iium.edu.my/58689/ C-Abl inhibition; a novel therapeutic target for Parkinson’s disease Abushouk, Abdelrahman Ibrahim Negida, Ahmed Abdelsalam Elshenawy, Rasha A Zein, Hossam Hammad, Ali M Menshawy, Ahmed Mohamed, Wael Mohamed Yousef R Medicine (General) 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. Bentham Science Publishers B.V. 2018 Article PeerReviewed application/pdf en http://irep.iium.edu.my/58689/1/58689_C-Abl%20inhibition.pdf application/pdf en http://irep.iium.edu.my/58689/2/58689_C-Abl%20inhibition_SCOPUS.pdf application/pdf en http://irep.iium.edu.my/58689/3/58689_C-Abl%20inhibition_WOS.pdf Abushouk, Abdelrahman Ibrahim and Negida, Ahmed and Abdelsalam Elshenawy, Rasha A and Zein, Hossam and Hammad, Ali M and Menshawy, Ahmed and Mohamed, Wael Mohamed Yousef (2018) C-Abl inhibition; a novel therapeutic target for Parkinson’s disease. CNS & Neurological disorders-Drug targets, 17 (1). pp. 14-21. ISSN 1871-5273 E-ISSN 1996-3181 http://www.eurekaselect.com/152890/article 10.2174/1871527316666170602101538
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English English English
topic	R Medicine (General)
spellingShingle	R Medicine (General) Abushouk, Abdelrahman Ibrahim Negida, Ahmed Abdelsalam Elshenawy, Rasha A Zein, Hossam Hammad, Ali M Menshawy, Ahmed Mohamed, Wael Mohamed Yousef C-Abl inhibition; a novel therapeutic target for Parkinson’s disease
description	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.
format	Article
author	Abushouk, Abdelrahman Ibrahim Negida, Ahmed Abdelsalam Elshenawy, Rasha A Zein, Hossam Hammad, Ali M Menshawy, Ahmed Mohamed, Wael Mohamed Yousef
author_facet	Abushouk, Abdelrahman Ibrahim Negida, Ahmed Abdelsalam Elshenawy, Rasha A Zein, Hossam Hammad, Ali M Menshawy, Ahmed Mohamed, Wael Mohamed Yousef
author_sort	Abushouk, Abdelrahman Ibrahim
title	C-Abl inhibition; a novel therapeutic target for Parkinson’s disease
title_short	C-Abl inhibition; a novel therapeutic target for Parkinson’s disease
title_full	C-Abl inhibition; a novel therapeutic target for Parkinson’s disease
title_fullStr	C-Abl inhibition; a novel therapeutic target for Parkinson’s disease
title_full_unstemmed	C-Abl inhibition; a novel therapeutic target for Parkinson’s disease
title_sort	c-abl inhibition; a novel therapeutic target for parkinson’s disease
publisher	Bentham Science Publishers B.V.
publishDate	2018
url	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
first_indexed	2023-09-18T21:23:00Z
last_indexed	2023-09-18T21:23:00Z
_version_	1777412007190855680

C-Abl inhibition; a novel therapeutic target for Parkinson’s disease

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