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

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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 languageEnglish
Pages (from-to)3610-3622
Number of pages13
JournalBrain
Volume138
Issue number12
DOIs
Publication statusPublished - 2015 Dec 1

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All Science Journal Classification (ASJC) codes

  • Clinical Neurology

Cite this

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