Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
CNS Neurosci Ther. 2024 Jul;30(7):e14880. doi: 10.1111/cns.14880.
Adenylyl cyclases (Adcys) catalyze the formation of cAMP, a secondary messenger essential for cell survival and neurotransmission pathways in the CNS. Adcy2, one of ten Adcy isoforms, is highly expressed in the CNS. Abnormal Adcy2 expression and mutations have been reported in various neurological disorders in both rodents and humans. However, due to the lack of genetic tools, loss-of-function studies of Adcy2 are scarce. In this review, we summarize recent findings on Adcy2 expression and function in neurological diseases. Specifically, we first introduce the biochemistry, structure, and function of Adcy2 briefly. Next, the expression and association of Adcy2 in human patients and rodent models of neurodegenerative diseases (Alzheimer's disease and Parkinson's disease), psychiatric disorders (Tourette syndrome, schizophrenia, and bipolar disorder), and other neurological conditions (stress-associated disorders, stroke, epilepsy, and Lesch-Nyhan Syndrome) are elaborated. Furthermore, we discuss the pros and cons of current studies as well as key questions that need to be answered in the future. We hope to provide a focused review on Adcy2 that promotes future research in the field.
腺苷酸环化酶（Adcys）催化 cAMP 的形成，cAMP 是中枢神经系统细胞存活和神经递质传递途径所必需的第二信使。Adcy2 是十种 Adcy 同工型之一，在中枢神经系统中高度表达。在啮齿动物和人类的各种神经疾病中，已经报道了异常的 Adcy2 表达和突变。然而，由于缺乏遗传工具，Adcy2 的功能丧失研究很少。在这篇综述中，我们总结了 Adcy2 在神经疾病中的表达和功能的最新发现。具体来说，我们首先简要介绍了 Adcy2 的生物化学、结构和功能。接下来，阐述了 Adcy2 在人类患者和神经退行性疾病（阿尔茨海默病和帕金森病）、精神障碍（妥瑞氏综合征、精神分裂症和双相情感障碍）和其他神经系统疾病（应激相关障碍、中风、癫痫和 Lesch-Nyhan 综合征）的啮齿动物模型中的表达和相关性。此外，我们还讨论了当前研究的优缺点以及未来需要回答的关键问题。我们希望提供一个关于 Adcy2 的重点综述，以促进该领域的未来研究。
