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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 589-601 |
| Number of pages | 13 |
| Journal | Journal of Parkinson's Disease |
| Volume | 7 |
| Issue number | 4 |
| DOIs | |
| State | Published - 2017 |
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Keywords
- Alpha-synuclein
- biomarkers
- c-Abl
- c-Abl inhibitors
- oxidative stress
- parkin
- Parkinson's disease
ASJC Scopus subject areas
- Clinical Neurology
- Cellular and Molecular Neuroscience
Cite this
C-Abl and Parkinson's Disease : Mechanisms and Therapeutic Potential. / Brahmachari, Saurav; Karuppagounder, Senthilkumar; Ge, Preston; Lee, Saebom; Dawson, Valina; Dawson, Ted M; Ko, Hanseok Seok.
In: Journal of Parkinson's Disease, Vol. 7, No. 4, 2017, p. 589-601.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - C-Abl and Parkinson's Disease
T2 - Mechanisms and Therapeutic Potential
AU - Brahmachari, Saurav
AU - Karuppagounder, Senthilkumar
AU - Ge, Preston
AU - Lee, Saebom
AU - Dawson, Valina
AU - Dawson, Ted M
AU - Ko, Hanseok Seok
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Alpha-synuclein
KW - biomarkers
KW - c-Abl
KW - c-Abl inhibitors
KW - oxidative stress
KW - parkin
KW - Parkinson's disease
UR - http://www.scopus.com/inward/record.url?scp=85032815362&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85032815362&partnerID=8YFLogxK
U2 - 10.3233/JPD-171191
DO - 10.3233/JPD-171191
M3 - Review article
C2 - 29103051
AN - SCOPUS:85032815362
VL - 7
SP - 589
EP - 601
JO - Journal of Parkinson's Disease
JF - Journal of Parkinson's Disease
SN - 1877-7171
IS - 4
ER -