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統合失調症における好気性解糖:発達的回復か、エネルギー崩壊か?
Onur Memetoglu1, Manu S Goyal2, Virginie-Anne Chouinard1
1McLean Hospital, Harvard Medical School, Belmont, MA, USA.
Molecular psychiatry
|January 31, 2026
まとめ
好気性解糖(AG)は、代謝プロセスであり、統合失調症(SZ)で上昇し、脳のエネルギー欠乏に対する代償反応である可能性があります。持続的なAGは脳機能を不安定にする可能性があり、新たな治療標的を提供します。
科学分野:
- 神経科学
- 代謝生物学
- 精神医学
背景:
- 好気性解糖(AG)、またはワールブルク効果は、細胞が酸素が存在する場合でも、解糖系を酸化的リン酸化(OxPhos)よりも優先的に使用する代謝プロセスです。
- 当初はがん細胞で観察されていましたが、AGは現在、生合成、神経可塑性、およびシナプス形成をサポートする広範な生理学的メカニズムとして理解されています。
研究 の 目的:
- 成人の統合失調症(SZ)におけるAGの上昇は、脳のバイオマスとミトコンドリア機能障害の減少に対する代償メカニズムを反映していると提案すること。
- AG、障害されたOxPhos、還元的ストレス、および脳における神経グリアカップリングの欠陥との関連を調査すること。
主な方法:
- 神経画像、分光法、および死後研究のレビュー。
- エネルギー恒常性に関連するオリゴデンドロサイト機能障害および白質損傷の分析。
- SZにおけるAGに関する現在の所見の視点に基づいた統合。
主要な成果:
- 証拠は、脳内のAGがOxPhosの障害、還元的ストレス、および神経グリア相互作用の損なわれと関連していることを示しています。
- オリゴデンドロサイト機能障害と白質異常は、脳のエネルギーバランスと接続性をさらに混乱させます。
- 持続的なAGは、修復をサポートする可能性がありますが、最終的にはシナプス機能を不安定にする可能性があります。
結論:
- SZにおけるAGは、発達的ニーズと成人期の代謝能力との間の不一致に対する不適応な応答を表す可能性があります。
- SZにおけるAGの持続性を理解することは、神経回路におけるエネルギーバランスを回復するための新しい戦略を特定する可能性があります。
- AGを標的とすることは、統合失調症の新しい治療法を提供する可能性があります。
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