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우울증과 항우울작용에 관한 p11(S100A10)의 역할

Role of p11 (S100A10) in Depression and Antidepressant Effects

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주제분류정신과학

초록

우울증(major depressive disorder)은 우울감, 의욕이나흥미 상실, 식욕저하나 체중감소, 수면장애, 에너지 고갈, 죄책감이나 무가치함, 집중력저하를 보이며 이로 인해 일상생활이나 사회생활에 심각한 지장을 주고 있다. 주요우울증 환자의 상당수가 재발률이 높고 잔류증상이 지속되며, 기능적인 손상과 함께 행복감이 떨어지는 등 예후가 좋지 않다. 수십 년 동안의 광범위한 연구에도 불구하고, 우울증 발병기전을 이해하는 데는 한계가 있다. 단가아민계(monoamine system) 에 영향을 미치는 현재 사용 중인 항우울제들은 대부분증상을 완화시키는 정도이며, 난치성 우울증이 많아 새로운약물 개발이 필요하다. 항우울제들은 1차적으로 세로토닌 및 노르에피네프린 증가에 즉각적인 효과를 보이지만 치료반응은 일반적으로 투여 3~4주 후에 발생한다. 이러한 치료지연은 유전자 발현과신경가소성(neural plasticity)의 장기적인 변화에 관여하는복잡한 후속기전들(downstream mechanisms)과 관련되어져 있을 것으로 추정된다. 이들 후속기전에 관여하는 여러 유전자들 중에서 보다 더 직접적으로 항우울제 반응의 표적이되는 유전자가 발견된다면 보다 더 효과적이고 빠른 효능을보일 수 있는 새로운 약물 개발에 도움이 될 것이다. 이에 저자는 본 글에서 최근에 우울증의 원인과 항우울제의 작용 기전 둘 다에 중요한 요소로 작용한다고 알려져 있는 p11 단백질을 소개하고자 한다.

Abstract

p11 protein (S100A10) is downregulated in depressive-like states of human and rodent. Antidepressant drug treatment increases p11 levels in rodent models. We reviewed studies demonstrating that p11 levels are regulated in depression and by antidepressant treatment and that p11 upregulation exerts antidepressant effects. Current studies on p11 underscore the importance of p11 as a potential antidepressant target.

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