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AMPA 수용체의 조절이 지니는 정신과적 의의

Psychiatric Implication for the Regulation of AMPA Receptor

이은이|오대영
대한생물정신의학회 (The Korean Society Of Biological Psychiatry)|2013.02|생물정신의학 (Journal of Korean Society of Biological Psychiatry)|제20권 제1호|pp. 1-5

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키워드

정신 질환시냅스AMPA글루타메이트 수용체PSD-95Glutamate receptorSynapsesPsychiatric disorder.
주제분류정신과학

초록

사고, 감정, 의식 등과 같은 인간 행동은 수많은 뇌 신경 세포 간의 연결인 시냅스를 통해서 이루어 진다. 최근에는 ‘syn-aptopathy’라는 개념이 도입되면서, 시냅스에서의 구조적 혹은 기능적 이상이 주요 정신 질환의 원인이 된다고 설명하고 있다.1) 여러 퇴행성 뇌질환의 경우 시냅스의 숫자나 기능이 감소하게 되고, 전반적인 신경 세포의 감소가 나타난다고 보고되고 있다.2) 또한 시냅스를 형성하거나 조절하는 단백질을 만들어내는 유전자들을 연구한 결과, 이들 단백질들이 시냅스의 기능에 이상을 유발하여 조현병 혹은 자폐증과 같은 정신 질환을 유발하는 것으로 알려져 있다.3)4)글루타메이트 수용체는 포유류의 뇌에서 광범위하게 발견되는 것으로 시냅스에서 매우 빠른 흥분성 신경 전달을 담당한다. 글루타메이트 수용체는 뇌에서 가장 많은 양을 차지하면서 가장 빠른 신호 전달을 하기 때문에 매우 일찍부터 다양한 연구가 시작되었다.5) 전기 생리학적인 연구뿐만 아니라 유전학적 연구를 통해서 글루타메이트 수용체의 변화는 정신 질환과 연관이 있음을 밝혔다.6)7)글루타메이트 수용체와 관련된 기전을 연구하는 것은 다양한 정신 질환의 기전을 밝히는데 매우 중요하다. 여기에서는 이와 관련된 생물학적인 개념 설명과 연관된 동물 모델 연구들을 소개하여 주요 정신 질환에 어떻게 기여하고 있는지를 설명하고자 한다

Abstract

Glutamate receptors are important components of synaptic transmission in the nervous system. Especially, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors mediate most abundant excitatory synaptic transmission in the brain. There is elaborate mechanism of regulation of AMPA receptors including protein synthesis/degradation, intracellular trafficking, exocytosis/endocytosis and protein modification. In recent studies, it is revealed that functional dysregulation of AMPA receptors are related to major psychiatric disorders. In this review, we describe the structure and function of AMPA receptors in the synapse. We will introduce three steps of mechanism involving trafficking of AMPA receptors to neuronal membrane, lateral diffusion into synapses and synaptic retention by membrane proteins and postsynaptic scaffold proteins. Lastly, we will describe recent studies showing that regulation of AMPA receptors is important pathophysiological mechanism in psychiatric disorders.

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