@article{28883068506443e19a217b5474e3842f,
title = "C-Abl and Parkinson's Disease: Mechanisms and Therapeutic Potential",
abstract = "Although the etiology of Parkinson's disease (PD) is poorly understood, oxidative stress has long been implicated in the pathogenesis of the disease. However, multifaceted and divergent signaling cascades downstream of oxidative stress have posed challenges for researchers to identify a central component of the oxidative stress-induced pathways causing neurodegeneration in PD. Since 2010, c-Abl-a non-receptor tyrosine kinase and an indicator of oxidative stress-has shown remarkable potential as a future promising drug target in PD therapeutics. Although, the constitutively active form of c-Abl, Bcr-Abl, has a long history in chronic myeloid leukemia and acute lymphocytic leukemia, the role of c-Abl in PD and relevant neurodegenerative diseases was completely unknown. Recently, others and we have identified and validated c-Abl as an important pathogenic mediator of the disease, where activated c-Abl emerges as a common link to various PD-related inducers of oxidative stress relevant to both sporadic and familial forms of PD and α-synucleinopathies. This review discusses the role of c-Abl in PD and the latest advancement on c-Abl as a drug target and as a prospective biomarker.",
keywords = "Alpha-synuclein, Parkinson's disease, biomarkers, c-Abl, c-Abl inhibitors, oxidative stress, parkin",
author = "Saurav Brahmachari and Karuppagounder, {Senthilkumar S.} and Preston Ge and Saebom Lee and Dawson, {Valina L.} and Dawson, {Ted M.} and Ko, {Han Seok}",
note = "Funding Information: The research discussed in this article is related to agents manufactured by Inhibikase Therapeutics. Dr. T.M. and V.L. Dawson are consultants to Inhibikase Therapeutics and own stock options in the company. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. The value of patents owned by Valted, LLC could be affected by this article. Also, Dr. T.M. and V.L. Dawson are founders This work was supported by grants from the National Institute of Neurological Disorders and Stroke (NINDS, NIH) (NS38377, the Morris K. Udall Parkinson{\textquoteright}s Disease Research Center, and NS082205 and NS098006) and the JPB Foundation. T.M. Dawson is the Leonard and Madlyn Abram-son Professor in Neurodegenerative Diseases. The authors acknowledge the joint participation by the Adrienne Helis Malvin Medical Research Foundation and the Diana Helis Henry Medical Research Foundation through their direct engagement in the continuous active conduct of medical research in conjunction with Johns Hopkins Hospital and the Johns Hopkins University School of Medicine and the foundations{\textquoteright} Parkinson{\textquoteright}s Disease Programs, H-1 and M-2014. I-Hsun Wu generated Fig. 1. Publisher Copyright: {\textcopyright} 2017-IOS Press and the authors. All rights reserved.",
year = "2017",
doi = "10.3233/JPD-171191",
language = "English (US)",
volume = "7",
pages = "589--601",
journal = "Journal of Parkinson's Disease",
issn = "1877-7171",
publisher = "IOS Press",
number = "4",
}