c-Abl Inhibitors Enable Insights into the Pathophysiology and Neuroprotection in Parkinson's Disease

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http://hdl.handle.net/10138/169270

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Lindholm , D , Pham , D D , Cascone , A , Eriksson , O , Wennerberg , K & Saarma , M 2016 , ' c-Abl Inhibitors Enable Insights into the Pathophysiology and Neuroprotection in Parkinson's Disease ' , Frontiers in aging neuroscience , vol. 8 , 254 . https://doi.org/10.3389/tnagi.2016.00254

Title: c-Abl Inhibitors Enable Insights into the Pathophysiology and Neuroprotection in Parkinson's Disease
Author: Lindholm, Dan; Pham, Dan D.; Cascone, Annunziata; Eriksson, Ove; Wennerberg, Krister; Saarma, Mart
Contributor organization: Medicum
Department of Biochemistry and Developmental Biology
Ove Eriksson-Rosenberg / Principal Investigator
Institute for Molecular Medicine Finland
Krister Wennerberg / Principal Investigator
Institute of Biotechnology
Mart Saarma / Principal Investigator
Date: 2016-10-26
Language: eng
Number of pages: 6
Belongs to series: Frontiers in aging neuroscience
ISSN: 1663-4365
DOI: https://doi.org/10.3389/tnagi.2016.00254
URI: http://hdl.handle.net/10138/169270
Abstract: Parkinson's disease (PD) is a progressive neurodegenerative disorder causing movement disabilities and several non-motor symptoms in afflicted patients. Recent studies in animal models of PD and analyses of brain specimen from PD patients revealed an increase in the level and activity of the non-receptor tyrosine kinase Abelson (c-Abl) in dopaminergic neurons with phosphorylation of protein substrates, such as alpha-synuclein and the E3 ubiquitin ligase, Parkin. Most significantly inhibition of c-Abl kinase activity by small molecular compounds used in the clinic to treat human leukemia have shown promising neuroprotective effects in cell and animal models of PD. This has raised hope that similar beneficial outcome may also be observed in the treatment of PD patients by using c-Abl inhibitors. Here we highlight the background for the current optimism, reviewing c-Abl and its relationship to pathophysiological pathways prevailing in PD, as well as discussing issues related to the pharmacology and safety of current c-Abl inhibitors. Clearly more rigorously controlled and well-designed trials are needed before the c-Abl inhibitors can be used in the neuroclinic to possibly benefit an increasing number of PD patients.
Subject: Parkinson's disease
alpha-synuclein
parkin
c-Abl
nilotinib
leukemia
CHRONIC MYELOID-LEUKEMIA
CYCLIN-DEPENDENT KINASE-5
ALPHA-SYNUCLEIN
BCR-ABL
LEWY BODIES
NILOTINIB
AUTOPHAGY
PHOSPHORYLATION
DEGRADATION
POTENT
3111 Biomedicine
3112 Neurosciences
3124 Neurology and psychiatry
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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