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中枢神经系统疾病中的抗 NMDA 和抗 AMPA 受体抗体:评估其病理性作用及向临床转化的转化医学研究方法。

Anti-NMDA and Anti-AMPA Receptor Antibodies in Central Disorders: Preclinical Approaches to Assess Their Pathological Role and Translatability to Clinic.

机构信息

Department of Pharmacy (DiFar), University of Genoa, Viale Cembrano 4, 16148 Genoa, Italy.

Center of Excellence for Biomedical Research, 3Rs Center, Department of Pharmacy (DiFar), University of Genoa, Viale Cembrano 4, 16148 Genoa, Italy.

出版信息

Int J Mol Sci. 2023 Oct 5;24(19):14905. doi: 10.3390/ijms241914905.

Abstract

Autoantibodies against NMDA and AMPA receptors have been identified in the central nervous system of patients suffering from brain disorders characterized by neurological and psychiatric symptoms. It has been demonstrated that these autoantibodies can affect the functions and/or the expression of the targeted receptors, altering synaptic communication. The importance to clarify, in preclinical models, the molecular mechanisms involved in the autoantibody-mediated effects has emerged in order to understand their pathogenic role in central disorders, but also to propose new therapeutic approaches for preventing the deleterious central consequences. In this review, we describe some of the available preclinical literature concerning the impact of antibodies recognizing NMDA and AMPA receptors in neurons. This review discusses the cellular events that would support the detrimental roles of the autoantibodies, also illustrating some contrasting findings that in our opinion deserve attention and further investigations before translating the preclinical observations to clinic.

摘要

自身抗体针对 NMDA 和 AMPA 受体已被鉴定在中枢神经系统的患者患有以神经和精神症状为特征的脑疾病。已经证明,这些自身抗体可以影响功能和/或表达的目标受体,改变突触通讯。重要的是要澄清,在临床前模型中,涉及自身抗体介导的作用的分子机制已经出现,以便了解它们在中枢疾病中的致病作用,但也提出了预防中枢损伤的新的治疗方法。在这篇综述中,我们描述了一些关于抗体识别 NMDA 和 AMPA 受体在神经元中的影响的临床前文献。本文讨论了支持自身抗体的有害作用的细胞事件,也说明了一些矛盾的发现,我们认为在将临床前观察结果转化为临床之前,这些发现值得关注和进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed5a/10573896/d35d1d427a3c/ijms-24-14905-g001.jpg

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