TRPV1 on astrocytes rescues nigral dopamine neurons in Parkinson's disease via CNTF

Jin H. Nam; Eun S. Park; So Yoon Won; Yu A. Lee; Kyoung I. Kim; Jae Y. Jeong; Jeong Y. Baek; Eun J. Cho; Minyoung Jin; Young C. Chung; Byoung D. Lee; Sung Hyun Kim; Eung Gook Kim; Kyunghee Byun; Bonghee Lee; Dong Ho Woo; C. Justin Lee; Sang R. Kim; Eugene Bok; Yoon Seong Kim; Tae Beom Ahn; Hyuk Wan Ko; Saurav Brahmachari; Olga Pletinkova; Juan C. Troconso; Valina L. Dawson; Ted M. Dawson; Byung K. Jin

doi:10.1093/brain/awv297

TRPV1 on astrocytes rescues nigral dopamine neurons in Parkinson's disease via CNTF

Jin H. Nam, Eun S. Park, So Yoon Won, Yu A. Lee, Kyoung I. Kim, Jae Y. Jeong, Jeong Y. Baek, Eun J. Cho, Minyoung Jin, Young C. Chung, Byoung D. Lee, Sung Hyun Kim, Eung Gook Kim, Kyunghee Byun, Bonghee Lee, Dong Ho Woo, C. Justin Lee, Sang R. Kim, Eugene Bok, Yoon Seong KimTae Beom Ahn, Hyuk Wan Ko, Saurav Brahmachari, Olga Pletinkova, Juan C. Troconso, Valina L. Dawson, Ted M. Dawson, Byung K. Jin

School of Medicine

Research output: Contribution to journal › Article › peer-review

55 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	3610-3622
Number of pages	13
Journal	Brain
Volume	138
Issue number	12
DOIs	https://doi.org/10.1093/brain/awv297
State	Published - Dec 1 2015

Keywords

Parkinson's disease
TRPV1
astrocyte
ciliary neurotrophic factor (CNTF)
dopamine neurons

ASJC Scopus subject areas

Clinical Neurology

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10.1093/brain/awv297

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Nam, J. H., Park, E. S., Won, S. Y., Lee, Y. A., Kim, K. I., Jeong, J. Y., Baek, J. Y., Cho, E. J., Jin, M., Chung, Y. C., Lee, B. D., Kim, S. H., Kim, E. G., Byun, K., Lee, B., Woo, D. H., Lee, C. J., Kim, S. R., Bok, E., ... Jin, B. K. (2015). TRPV1 on astrocytes rescues nigral dopamine neurons in Parkinson's disease via CNTF. Brain, 138(12), 3610-3622. https://doi.org/10.1093/brain/awv297

Nam, JH, Park, ES, Won, SY, Lee, YA, Kim, KI, Jeong, JY, Baek, JY, Cho, EJ, Jin, M, Chung, YC, Lee, BD, Kim, SH, Kim, EG, Byun, K, Lee, B, Woo, DH, Lee, CJ, Kim, SR, Bok, E, Kim, YS, Ahn, TB, Ko, HW, Brahmachari, S, Pletinkova, O, Troconso, JC, Dawson, VL , Dawson, TM & Jin, BK 2015, 'TRPV1 on astrocytes rescues nigral dopamine neurons in Parkinson's disease via CNTF', Brain, vol. 138, no. 12, pp. 3610-3622. https://doi.org/10.1093/brain/awv297

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title = "TRPV1 on astrocytes rescues nigral dopamine neurons in Parkinson's disease via CNTF",

abstract = "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.",

keywords = "Parkinson's disease, TRPV1, astrocyte, ciliary neurotrophic factor (CNTF), dopamine neurons",

author = "Nam, {Jin H.} and Park, {Eun S.} and Won, {So Yoon} and Lee, {Yu A.} and Kim, {Kyoung I.} and Jeong, {Jae Y.} and Baek, {Jeong Y.} and Cho, {Eun J.} and Minyoung Jin and Chung, {Young C.} and Lee, {Byoung D.} and Kim, {Sung Hyun} and Kim, {Eung Gook} and Kyunghee Byun and Bonghee Lee and Woo, {Dong Ho} and Lee, {C. Justin} and Kim, {Sang R.} and Eugene Bok and Kim, {Yoon Seong} and Ahn, {Tae Beom} and Ko, {Hyuk Wan} and Saurav Brahmachari and Olga Pletinkova and Troconso, {Juan C.} and Dawson, {Valina L.} and Dawson, {Ted M.} and Jin, {Byung K.}",

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doi = "10.1093/brain/awv297",

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T1 - TRPV1 on astrocytes rescues nigral dopamine neurons in Parkinson's disease via CNTF

AU - Nam, Jin H.

AU - Park, Eun S.

AU - Won, So Yoon

AU - Lee, Yu A.

AU - Kim, Kyoung I.

AU - Jeong, Jae Y.

AU - Baek, Jeong Y.

AU - Cho, Eun J.

AU - Jin, Minyoung

AU - Chung, Young C.

AU - Lee, Byoung D.

AU - Kim, Sung Hyun

AU - Kim, Eung Gook

AU - Byun, Kyunghee

AU - Lee, Bonghee

AU - Woo, Dong Ho

AU - Lee, C. Justin

AU - Kim, Sang R.

AU - Bok, Eugene

AU - Kim, Yoon Seong

AU - Ahn, Tae Beom

AU - Ko, Hyuk Wan

AU - Brahmachari, Saurav

AU - Pletinkova, Olga

AU - Troconso, Juan C.

AU - Dawson, Valina L.

AU - Dawson, Ted M.

AU - Jin, Byung K.

PY - 2015/12/1

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N2 - 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.

AB - 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.

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KW - astrocyte

KW - ciliary neurotrophic factor (CNTF)

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TRPV1 on astrocytes rescues nigral dopamine neurons in Parkinson's disease via CNTF

Abstract

Keywords

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