Adenylate cyclase 1 (ADCY1), also known as AC1, is a member of the ADCY superfamily. It is primarily expressed in the brain and is responsible for catalyzing ATP to cyclic AMP (cAMP), a secondary messenger that regulates numerous cellular activities. cAMP can bind to cAMP-dependent protein kinases (PKAs), cAMP-activated guanine exchange factors (EPACs), and cyclic nucleotide-gated channels (CNGs) to regulate cellular transport and sensory signal transduction [1].

In gene knockout (KO) mouse models, Adcy1 -/- mice showed protocol-dependent deficits in long-term potentiation (LTP) at the Schaffer collateral-CA1 synapses, and long-term depression (LTD) required ADCY1. ADCY1 was also found to be essential for the formation of both initial and reversal memory, indicating its role in regulating synaptic and cognitive flexibility [2]. In glioma research, overexpression of CUX2 promoted ADCY1 transcription, which delayed glioma cell migration, proliferation, and invasion, suggesting ADCY1's potential as a regulator in glioma malignancy [3]. In lung cancer, ADCY1 polymorphisms are associated with platinum-based chemotherapy resistance, and ADCY1 can affect cisplatin resistance by regulating cell proliferation, apoptosis, and the cell cycle [4].

In conclusion, ADCY1 is crucial for cAMP-mediated cellular regulation. Studies using KO mouse models have revealed its significance in synaptic plasticity, cognitive function, and in disease conditions such as glioma and lung cancer, providing insights into its potential as a therapeutic target in these disease areas.

References:

1. Zou, Ting, Liu, Junyan, She, Li, Zhou, Honghao, Liu, Zhaoqian. 2019. A perspective profile of ADCY1 in cAMP signaling with drug-resistance in lung cancer. In Journal of Cancer, 10, 6848-6857. doi:10.7150/jca.36614. https://pubmed.ncbi.nlm.nih.gov/31839819/

2. Zhang, Ming, Wang, Hongbing. 2023. Ca2+-stimulated ADCY1 and ADCY8 regulate distinct aspects of synaptic and cognitive flexibility. In Frontiers in cellular neuroscience, 17, 1215255. doi:10.3389/fncel.2023.1215255. https://pubmed.ncbi.nlm.nih.gov/37465213/

3. Yao, Guojun, Le, Shihai, Min, Sufang, Cai, Chuanxing, Deng, Ling. 2022. CUX2 prevents the malignant progression of gliomas by enhancing ADCY1 transcription. In Experimental brain research, 240, 3153-3165. doi:10.1007/s00221-022-06481-w. https://pubmed.ncbi.nlm.nih.gov/36242624/

4. Zou, Ting, Liu, Jun-Yan, Liu, Zhao-Qian, Xiao, Di, Chen, Juan. 2024. The Role of ADCY1 in Regulating the Sensitivity of Platinum-Based Chemotherapy in NSCLC. In Pharmaceuticals (Basel, Switzerland), 17, . doi:10.3390/ph17091118. https://pubmed.ncbi.nlm.nih.gov/39338283/