반응성 알데히드종

Reactive aldehyde species
흔한 질환 관련 소염성 RASP인 4-히드록시노네날

반응성 알데하이드(RASP)는 반응성 알데하이드라고도 하며 일반적으로 독성이 있거나 염증을 촉진하는 친전자성 유기 알데하이드 분자의 종류를 말합니다.RASP는 특히 [1]단백질에서 시프 염기 형성을 통해 아민기와 티올기와 공유 반응한다.RASP는 MAP 키나제, 단백질 키나제 C 및 사이토카인 방출 및 [3]염증의 다른 측면을 증강하는 다른 단백질로 기술된 것처럼 친전자 응답 프로테옴에 대한 임계 결합량에 따라 단백질 기능을 [2]수정한다.RASP가 단백질에 결합하면 NF-kB 활성화,[4] 자가항체 형성,[5] 염증체 활성화 [6]및 스캐빈저 수용체 [7]A의 활성화로 이어질 수 있다. RASP는 알코올의 [8]산화, 폴리아민 대사 및 지질 과산화 [1]등의 다양한 과정을 통해 형성된다.RASP는 단백질 및 글루타티온 등의 다른 아민 또는 티올 함유 분자에 결합하는 것 외에 알데히드탈수소효소[8] 또는 알데히드환원효소에 [9]의해 대사된다.RASP의 독성 때문에, 알데히드 탈수소효소의 소수의 유전자 돌연변이만이 생존 가능한 자손을 허용하고, 그 결과 셰그렌-라르손 증후군,[8] 숙신성 반알데히드 탈수소효소 결핍증,[10] 그리고 다른 희귀 질병이 발생한다.

아크로레인, 크로톤알데히드, 아세트알데히드, 헥사날 [11]등 많은 다른 질병들이 [1]설명되었지만, 가장 일반적으로 보고된 두 가지 질병 관련 염증성 RASP는 말론디알데히드와 4-히드록시노네날이다.RASP의 독성에는 돌연변이 유발성, 골재 형성 및 일반 세포 [1][12]독성이 포함된다.

예를 들어, 말론디알데히드는 천식,[13] 건선,[14][15] 그리고 안구건조증을 포함한 많은 염증성 및 자가면역성 질병과 연관되어 왔다.레티날알데히드는 [16]독성을 방지하기 위해 단백질 샤페론에 크게 의존하지만 동물에서 필수적인 비염증 생리 기능에 영향을 미치는 것으로 보인다.

임상시험에서 RASP 억제제 reproxalap은 비감염성 전포막염,[17][20][21][22] 안구건조증[18][19] 및 알레르기 결막염 환자의 염증을 완화시키는 것으로 나타났다.

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