ミトコンドリア疾患の治療法としての低酸素

Isha H Jain¹, Luca Zazzeron², Rahul Goli¹

¹Department of Molecular Biology and Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA, USA. Department of Systems Biology, Harvard Medical School, Boston, MA, USA. Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Science (New York, N.Y.)

|February 27, 2016

まとめ

ミトコンドリアの毒性から保護する. この発見は,酸素不足に身体の適応を模倣することで,ミトコンドリア疾患と老化に対する潜在的な治療戦略を提供します.

科学分野:

生物化学
遺伝学
細胞生物学

背景:

ミトコンドリア呼吸器連鎖 (RC) の欠陥は重篤なヒト疾患を引き起こし,老化に寄与する.
RC機能障害に対する保護因子を特定することは,治療開発にとって極めて重要です.

研究の目的:

ゲノム全体のスクリーンを用いてミトコンドリア呼吸連鎖阻害から保護する要因を特定する.
ミトコンドリア機能障害における低酸素反応の治療の可能性を調査する.

主な方法:

RC阻害中の保護因子を特定するために,全ゲノムCas9媒介スクリーン.
細胞とゼブラフィッシュのモデルにおける低酸素反応の遺伝的および小分子活性化
リー症候群の遺伝的マウスモデルにおける慢性低酸素効果の評価

主要な成果:

低酸素反応は,RC阻害に対する重要な保護メカニズムとして特定されました.
低酸素反応の活性化により,前臨床モデルではミトコンドリアの毒性に対する保護が認められた.
慢性低酸素症は,リー症候群のマウスモデルで生存率と疾患のパラメータを大幅に改善しました.

結論:

低酸素反応はミトコンドリア機能障害に対する有望な内生的な保護メカニズムです.
ミトコンドリア疾患の治療に効く可能性を示しています.
ヒトのミトコンドリア疾患に対する低毒性治療の検討のため,さらなる臨床前研究が必要である.

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