Normandie Univ, UNICAEN, INSERM, CYCERON, COMETE, 14000 Caen, France.
Normandie Univ, UNICAEN, INSERM, CYCERON, COMETE, 14000 Caen, France.
Biochim Biophys Acta Proteins Proteom. 2021 Jan;1869(1):140542. doi: 10.1016/j.bbapap.2020.140542. Epub 2020 Sep 18.
Among aging-induced impairments, those affecting cognitive functions certainly represent one the most major challenge to face to improve elderly quality of life. In last decades, our knowledge on changes in the morphology and function of neuronal networks associated with normal and pathological brain aging has rapidly progressed, initiating the development of different pharmacological and behavioural strategies to alleviate cognitive aging. In particular, experimental evidences have accumulated indicating that the communication between neurons and its plasticity gradually weakens with aging. Because of its pivotal role for brain functional plasticity, the N-Methyl‑d-Aspartate receptor subtype of glutamate receptors (NMDAr) has gathered much of the experimental interest. NMDAr activation is regulated by many mechanisms. Among is the mandatory binding of a co-agonist, such as the amino acid d-serine, in order to activate NMDAr. This mini-review presents the most recent information indicating how d-serine could contribute to mechanisms of physiological cognitive aging and also considers the divergent views relative of the role of the NMDAr co-agonist in Alzheimer's disease.
在与衰老相关的功能衰退中，那些影响认知功能的衰退无疑是改善老年人生活质量所面临的最大挑战之一。在过去几十年中，我们对与正常和病理性脑衰老相关的神经网络形态和功能变化的了解迅速发展，从而启动了不同的药理学和行为策略的开发，以减轻认知衰老。特别是，越来越多的实验证据表明，神经元之间的通讯及其可塑性随着衰老而逐渐减弱。由于其对大脑功能可塑性的关键作用，谷氨酸受体的 N-甲基-D-天冬氨酸受体亚基（NMDAr）引起了广泛的实验关注。NMDAr 的激活受到许多机制的调节。其中之一是必需结合共激动剂，例如氨基酸 D-丝氨酸，以激活 NMDAr。这篇综述介绍了最新的信息，表明 D-丝氨酸如何有助于生理认知衰老的机制，并考虑了相对阿尔茨海默病中 NMDAr 共激动剂作用的不同观点。
