TRPV1 on astrocytes rescues nigral dopamine neurons in Parkinson's disease via CNTF.
Currently there is no neuroprotective or neurorestorative therapy for Parkinson's disease. Here we report that transient receptor potential vanilloid 1 (TRPV1) on astrocytes mediates endogenous production of ciliary neurotrophic factor (CNTF), which prevents the active degeneration of dopamine neurons and leads to behavioural recovery through CNTF receptor alpha (CNTFRα) on nigral dopamine neurons in both the MPP(+)-lesioned or adeno-associated virus α-synuclein rat models of Parkinson's disease. Western blot and immunohistochemical analysis of human post-mortem substantia nigra from Parkinson's disease suggests that this endogenous neuroprotective system (TRPV1 and CNTF on astrocytes, and CNTFRα on dopamine neurons) might have relevance to human Parkinson's disease. Our results suggest that activation of astrocytic TRPV1 activates endogenous neuroprotective machinery in vivo and that it is a novel therapeutic target for the treatment of Parkinson's disease.
1 Department of Biochemistry and Molecular Biology, Department of Neuroscience, Neurodegeneration Control Research Centre, School of Medicine Kyung Hee University, Seoul 130-701, Korea.
Jin H
JH
Nam
1 Department of Biochemistry and Molecular Biology, Department of Neuroscience, Neurodegeneration Control Research Centre, School of Medicine Kyung Hee University, Seoul 130-701, Korea.
Eun S
ES
Park
2 Department of Biochemistry and Signaling Disorder Research Centre, College of Medicine, Chungbuk National University, Cheongju 361-763, Korea.
So-Yoon
SY
Won
1 Department of Biochemistry and Molecular Biology, Department of Neuroscience, Neurodegeneration Control Research Centre, School of Medicine Kyung Hee University, Seoul 130-701, Korea.
Yu A
YA
Lee
1 Department of Biochemistry and Molecular Biology, Department of Neuroscience, Neurodegeneration Control Research Centre, School of Medicine Kyung Hee University, Seoul 130-701, Korea.
Kyoung I
KI
Kim
1 Department of Biochemistry and Molecular Biology, Department of Neuroscience, Neurodegeneration Control Research Centre, School of Medicine Kyung Hee University, Seoul 130-701, Korea.
Jae Y
JY
Jeong
1 Department of Biochemistry and Molecular Biology, Department of Neuroscience, Neurodegeneration Control Research Centre, School of Medicine Kyung Hee University, Seoul 130-701, Korea.
Jeong Y
JY
Baek
1 Department of Biochemistry and Molecular Biology, Department of Neuroscience, Neurodegeneration Control Research Centre, School of Medicine Kyung Hee University, Seoul 130-701, Korea.
Eun J
EJ
Cho
1 Department of Biochemistry and Molecular Biology, Department of Neuroscience, Neurodegeneration Control Research Centre, School of Medicine Kyung Hee University, Seoul 130-701, Korea.
Minyoung
M
Jin
1 Department of Biochemistry and Molecular Biology, Department of Neuroscience, Neurodegeneration Control Research Centre, School of Medicine Kyung Hee University, Seoul 130-701, Korea.
Young C
YC
Chung
1 Department of Biochemistry and Molecular Biology, Department of Neuroscience, Neurodegeneration Control Research Centre, School of Medicine Kyung Hee University, Seoul 130-701, Korea.
Byoung D
BD
Lee
1 Department of Biochemistry and Molecular Biology, Department of Neuroscience, Neurodegeneration Control Research Centre, School of Medicine Kyung Hee University, Seoul 130-701, Korea.
Sung Hyun
SH
Kim
2 Department of Biochemistry and Signaling Disorder Research Centre, College of Medicine, Chungbuk National University, Cheongju 361-763, Korea.
Eung-Gook
EG
Kim
3 Center for Genomics and Proteomics, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon 406-840, Korea.
Kyunghee
K
Byun
3 Center for Genomics and Proteomics, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon 406-840, Korea.
Bonghee
B
Lee
4 Center for Neuroscience and Functional Connectomics, Brain Science Institute, Korea Institute of Science and Technology, Seoul 130-701, Korea.
Dong Ho
DH
Woo
4 Center for Neuroscience and Functional Connectomics, Brain Science Institute, Korea Institute of Science and Technology, Seoul 130-701, Korea.
C Justin
CJ
Lee
5 School of Life Sciences, BK21 Plus KNU Creative Bio Research Group, Kyungpook National University, Daegu 702-701, Korea.
Sang R
SR
Kim
1 Department of Biochemistry and Molecular Biology, Department of Neuroscience, Neurodegeneration Control Research Centre, School of Medicine Kyung Hee University, Seoul 130-701, Korea 6 Burnett School of Biomedical Sciences, College of Medicine University of Central Florida, FL 32827, USA.
Eugene
E
Bok
6 Burnett School of Biomedical Sciences, College of Medicine University of Central Florida, FL 32827, USA.
Yoon-Seong
YS
Kim
7 Department of Neurology, School of Medicine, Kyung Hee University, Seoul 130-701, Korea.
Tae-Beom
TB
Ahn
1 Department of Biochemistry and Molecular Biology, Department of Neuroscience, Neurodegeneration Control Research Centre, School of Medicine Kyung Hee University, Seoul 130-701, Korea.
Hyuk Wan
HW
Ko
8 Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 9 Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA 10 Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Saurav
S
Brahmachari
11 Departments of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Olga
O
Pletinkova
9 Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA 11 Departments of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Juan C
JC
Troconso
8 Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 9 Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA 12 Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA 13 Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA 14 Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130-2685, USA.
Valina L
VL
Dawson
8 Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 9 Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA 10 Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA 12 Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA 14 Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130-2685, USA 15 Diana Helis Henry Medical Research Foundation, New Orleans, LA 70130-2685, USA.
Ted M
TM
Dawson
1 Department of Biochemistry and Molecular Biology, Department of Neuroscience, Neurodegeneration Control Research Centre, School of Medicine Kyung Hee University, Seoul 130-701, Korea bkjin@khu.ac.kr.
Byung K
BK
Jin
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism*; D053739:Ciliary Neurotrophic Factor Receptor alpha Subunit / Q000378:metabolism; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D009416:Nerve Regeneration; D000066829:Neuroprotection; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D050916:TRPV Cation Channels / Q000378:metabolism
D020934:Ciliary Neurotrophic Factor; D053739:Ciliary Neurotrophic Factor Receptor alpha Subunit; D050916:TRPV Cation Channels; C494484:TRPV1 receptor
Parkinson’s disease; TRPV1; astrocyte; ciliary neurotrophic factor (CNTF); dopamine neurons