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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 504 - 515 (12page)
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초록· 키워드
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Parkinson’s disease (PD) is one of the late-onset neurodegenerative movement disorder. Major pathological markers of PD include progressive loss of dopaminergic neurons, Lewy body formation, genetic mutations, and environmental factors. Epigenetic regulation of specific gene expression via impaired histone acetylation is associated with neuronal dysfunction in various neurodegenerative diseases. In this study, we hypothesized that histone deacetylase (HDAC) inhibitor, valproic acid (VPA), can improve motor function by enhancing cell survival in PD genetic model mice with LRRK2 R1441G mutation. To address this question, we administered VPA in LRRK2 R1441G transgenic mice to determine whether VPA affects 1) histone acetylation and HDAC expression, 2) dopaminergic neuron survival, 3) inflammatory responses, 4) motor or non-motor symptoms. As results, VPA administration increased histone acetylation level and the number of tyrosine hydroxylase (TH) positive neurons in substantia nigra of LRRK2 R1441G mice. VPA reduced iba-1 positive activated microglia and the mRNA levels of pro-inflammatory marker genes in LRRK2 R1441G mice. In addition, VPA induced the improvement of PD-like motor and non-motor behavior in LRRK2 R1441G mice. These data suggest that the inhibition of HDAC can be further studied as potential future therapeutics for PD
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참고문헌 (56)
참고문헌 신청
Spillantini MG / 1997 / Alpha-synuclein in Lewy bodies / Nature 388:839~840
Baba M / 1998 / Aggregation of alphasynuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies / Am J Pathol 152:879~884
Polymeropoulos MH / 1997 / Mutation in the alpha-synuclein gene identified in families with Parkinson's disease / Science 276:2045~2047
Kitada T / 1998 / Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism / Nature 392:605~608
Lockhart PJ / 2004 / DJ-1 mutations are a rare cause of recessively inherited early onset parkinsonism mediated by loss of protein function / J Med Genet 41:e22
Baba M / 1998 / Aggregation of alphasynuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies / Am J Pathol 152:879~884
Polymeropoulos MH / 1997 / Mutation in the alpha-synuclein gene identified in families with Parkinson's disease / Science 276:2045~2047
Kitada T / 1998 / Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism / Nature 392:605~608
Lockhart PJ / 2004 / DJ-1 mutations are a rare cause of recessively inherited early onset parkinsonism mediated by loss of protein function / J Med Genet 41:e22
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