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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2021.1
- 수록면
- 113 - 119 (7page)
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초록· 키워드
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The cause of Parkinson’s disease has been traditionally believed to be the dopaminergic neuronal death in the substantia nigra pars compacta (SNpc). This traditional view has been recently challenged by the proposal that reactive astrocytes serve as key players in the pathology of Parkinson’s dis ease through excessive GABA release. This aberrant astrocytic GABA is synthesized by the enzymatic action of monoamine oxidase B (MAOB), whose pharmacological inhibition and gene-silencing are reported to significantly alleviate parkinsonian motor symptoms in animal models of Parkinson’s disease. However, whether genetic ablation and over-expression of MAOB can bidirectionally regulate parkinsonian motor symptoms has not been tested. Here we demonstrate that genetic ablation of MAOB blocks the MPTP-induced augmentation of astrocytic GABA-mediated tonic inhibition of neighboring dopaminergic neurons as well as parkinsonian motor symptoms, indicating the necessity of MAOB for parkinso nian motor symptoms. Furthermore, we demonstrate that GFAP-MAOB transgenic mice, in which MAOB is over-expressed under the GFAP pro moter for astrocyte-specific over-expression, display exacerbated MPTP-induced tonic inhibition and parkinsonian motor symptoms compared to wild-type mice, indicating the importance of astrocytic MAOB for parkinsonian motor symptoms. Our study provides genetic pieces of evidence for the causal link between the pathological role of astrocytic MAOB-dependent tonic GABA synthesis and parkinsonian motor symptoms.
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참고문헌 (20)
참고문헌 신청
Dickson DW / 2012 / Parkinson's disease and Parkinsonism : neuropathology / Cold Spring Harb Perspect Med 2:a009258
Urso D / 2020 / Improving the delivery of levodopa in Parkinson's disease : a review of approved and emerging therapies / CNS Drugs 34:1149~1163
LeWitt PA / 2015 / Levodopa therapy for Parkinson's disease : pharmacokinetics and pharmacodynamics / Mov Disord 30:64~72
Teismann P / 2003 / Pathogenic role of glial cells in Parkinson's disease / Mov Disord 18:121~129
Liberatore GT / 1999 / Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease / Nat Med 5:1403~1409
Urso D / 2020 / Improving the delivery of levodopa in Parkinson's disease : a review of approved and emerging therapies / CNS Drugs 34:1149~1163
LeWitt PA / 2015 / Levodopa therapy for Parkinson's disease : pharmacokinetics and pharmacodynamics / Mov Disord 30:64~72
Teismann P / 2003 / Pathogenic role of glial cells in Parkinson's disease / Mov Disord 18:121~129
Liberatore GT / 1999 / Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease / Nat Med 5:1403~1409
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