c-Abl and Parkinson's Disease: Mechanisms and Therapeutic Potential

被引：72

作者：

Brahmachari, Saurav ^{[1
,2
,3
,7
]}

Karuppagounder, Senthilkumar S. ^{[1
,2
,3
,7
]}

Ge, Preston ^{[1
,2
,3
,7
]}

Lee, Saebom ^{[1
,2
,3
]}

Dawson, Valina L. ^{[1
,2
,3
,4
,5
,7
]}

Dawson, Ted M. ^{[1
,2
,3
,5
,6
,7
]}

Ko, Han Seok ^{[1
,2
,5
,8
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Neuroregenerat Program, 733 North Broadway,Suite 731, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Stem Cell Program, 733 North Broadway,Suite 731, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA

[6] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

[7] Adrienne Helis Malvin Med Res Fdn, New Orleans, LA USA

[8] Diana Helis Henry Med Res Fdn, New Orleans, LA USA

来源：

JOURNAL OF PARKINSONS DISEASE | 2017年 / 7卷 / 04期

关键词：

Alpha-synuclein; biomarkers; c-Abl; c-Abl inhibitors; oxidative stress; parkin; Parkinson's disease; CEREBROSPINAL-FLUID BIOMARKERS; PATHOLOGICAL ALPHA-SYNUCLEIN; TYROSINE KINASE INHIBITOR; CHRONIC MYELOID-LEUKEMIA; OXIDATIVE STRESS; BCR-ABL; CELLULAR-RESPONSE; PROTEIN-KINASE; COGNITIVE IMPAIRMENT; CSF BIOMARKERS;

D O I：

10.3233/JPD-171191

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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 alpha-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.

引用

页码：589 / 601

页数：13

共 91 条

[1] Activation of the neuronal c-Abl tyrosine kinase by amyloid-β-peptide and reactive oxygen species [J].