Unique Mechanism of Action of Alzheimer's Drugs on Brain Nicotinic Acetylcholine Receptors and NMDA receptors

Alzheimer's disease is a neurological disorder characterized by cognitive deficit and loss of memory. While a large number of studies suggest involvement of b-amyloid, tau proteins and other factors in the etiology of Alzheimer's disease, no definitive causes of the disease have been discovered yet. Thus, there is no way to cure this serious disorder, and only symptomatic drug treatment is being used. In the brain of Alzheimer's disease patients, both nicotinic acetylcholine receptors and NMDA receptors are known to be down-regulated. Several Alzheimer's drugs inhibit cholinesterase thereby stimulating the cholinergic system. However, we have recently demonstrated that some of these drugs also stimulate the NMDA system. Therefore, these drugs bring back the down-regulated nicotinic receptors and NMDA receptors to the normal levels thereby improving the learning, cognition and memory of Alzheimer's disease patients.

楢橋先生は１９６４、６７年に、フグ毒であるテトロドトキシン（TTX）や貝毒であるサキシトキシン（STX）の薬理学的作用機序を世界に先駆け解明するという歴史的業績を挙げられました。この研究により活動電位のイオン機構が直接的に明らかとなり、その後の神経科学の分野に大きな影響を与えるきわめて重要な研究成果です。楢橋先生は、現在も世界の第一線でご活躍されており、神経細胞に発現するアセチルコリン受容体、GABAA受容体、NMDA受容体などの薬理学的な調節機構について精力的に研究をされ、多くの新しい知見を発表されています。今回、医科研でご講演頂く機会に恵まれましたので、皆様ぜひご参集下さい。