アルツハイマー病と正常なニューロンの体内APP遺伝子再結合

Ming-Hsiang Lee¹, Benjamin Siddoway¹, Gwendolyn E Kaeser^1,2

¹Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.

Nature

|November 23, 2018

まとめ

人間のニューロンは体内遺伝子の再結合を示し,APP遺伝子から多様なゲノムcDNAを生成する. アルツハイマー病に関連したこのプロセスは脳の可塑性や細胞の多様性に関する新しいメカニズムを示唆しています

科学分野:

神経科学
遺伝学
分子生物学

背景:

人間の脳の複雑さは静的なゲノムによって支配されていると考えられています
非繁殖性細胞のDNAを変化させるソマティック遺伝子再結合は,以前は脳で文書化されていなかった.

研究の目的:

ヒトのニューロンの体内遺伝子の再結合を研究する
アルツハイマー病に関連したAPP遺伝子における再結合の性質と影響を記述する.

主な方法:

単一のニューロン内の変異性ゲノムcDNA (gencDNA) を検出するためのDNA in situ混合化.
転写,DNAの断裂,逆転写酵素の活性,および年齢を含むメカニズム研究.
健康な個人とアルツハイマー病患者のニューロンの比較分析

主要な成果:

人間のニューロンにおける APP 遺伝子のモザイク再結合が発見され,何千もの内向的な gencDNA が生成された.
gencDNAは様々な変異を伴う全長型および小型の変異を含む多様な形態を示しています.
アルツハイマー病患者のニューロンにおいて,遺伝子DNAの多様性と特定の家族性アルツハイマー病変異が観察された.

結論:

RNAのレトロ挿入によるニューロン遺伝子の再結合は,細胞の多様性に寄与し,神経活動の記録に役割を果たす可能性があります.
このメカニズムは学習,記憶,可塑性,アルツハイマー病などの脳疾患の理解に重要な意味を持ちます

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