ナカヤマ　ケンタロウ   NAKAYAMA KENTARO   中山　健太郎    所属   関西医科大学  神経内科学講座    職種   助教
言語種別	英語
発表タイトル	Immunohistochemical analysis of BRCA1 in Parkinson's disease
会議名	第62回日本神経学会学術大会
学会区分	全国規模の学会
発表形式	ポスター掲示
講演区分	一般
発表者・共同発表者	◎中村正孝, 中山健太郎, 片岡優子, 森勢諭, 村上綾, 國枝武伸, 金子鋭, 藥師寺祐介
発表年月日	2021/05/21
開催地 （都市, 国名）	京都
概要	Background: BRCA1 plays important roles in several biological events during the DNA damage response (DDR). BRCA1 is phosphorylated at multiple sites by several kinases in response to DNA damage. Recently, we reported that BRCA1 and phosphorylated BRCA1 (pBRCA1) accumulate in neuronal and glial tau-positive inclusions in several tauopathies. It has also been reported that DNA damage and abnormalities in DNA repair are implicated in the pathogenesis of Parkinson's disease (PD). Aims: To investigate whether the expression of BRCA1, its binding partner BARD1, and another DDR protein, 53BP is altered in PD. Methods: We examined paraffin-embedded sections of midbrain and medulla oblongata from 5 PD and 5 control patients by immunohistochemical analysis. Results: In control patients, pBRCA1 (1423) immunoreactivity was faintly present in the nucleus of neurons, whereas BRCA1, BARD1, and pBRCA1 (1524) immunoreactivity was absent. In PD patients, BARD1 and pBRCA1 (1423) immunoreactivity was mainly present in the core of Lewy bodies and Lewy neurites. On the other hand, BRCA1 and pBRCA1 (1524) immunoreactive deposition was rarely observed in the nucleus and cytoplasm of neurons. There was no difference in the subcellular localization of 53BP1 between control and PD patients. Double immunofluorescence for pBRCA1 (1423) or BARD1 and alpha-synuclein revealed co-localization of these proteins within Lewy bodies and Lewy neurites. Conclusions: Our present results suggest that the accumulation of pBRCA1 (1423) and BARD1 could be an important event in the pathogenesis of PD.