Ak5-KO Mouse

Ak5, or adenylate kinase 5, is a cytosolic protein belonging to the adenylate kinase family. It catalyzes reversible phosphate transfer between adenine nucleotides, thus being involved in cellular energy metabolism, nucleotide metabolism, and energy regulation [4,5]. It may also play a role in cellular differentiation [5].

In gastric cancer, knocking down Ak5 in cell lines significantly inhibited proliferation and autophagy, and increased apoptosis, suggesting it could be a potential prognostic marker and therapeutic target [1]. In anti-Ak5 limbic encephalitis, patients often show severe episodic amnesia, frequently associated with depression, weight loss, asthenia, and anorexia. CSF abnormalities and temporal lobe hyperintensities are common, and the disease has a poor response to immunotherapy, likely due to a distinct T cell-mediated pathogenesis with major cytotoxicity-induced apoptosis [2]. In colorectal adenocarcinoma, Ak5 promoter hypermethylation down-regulates gene expression, and Ak5 regulates the phosphorylated AMPK and mTOR phosphorylation, inhibiting cell migration and invasion [4]. In Alzheimer's disease, in oligodendrocytes treated with Aβ1-42, overexpression of Ak5 activated the AMPK signaling pathway, inhibiting neuroinflammation and apoptosis, while low levels of Ak5 expression during early differentiation triggered inflammatory responses and increased apoptosis [3].

In summary, Ak5 is crucial in cellular energy-related processes. Research on Ak5, including through functional studies such as gene knockdown in cell lines, has revealed its roles in various diseases, including gastric cancer, anti-Ak5 limbic encephalitis, colorectal adenocarcinoma, and Alzheimer's disease, suggesting its potential as a prognostic marker and therapeutic target in these disease areas.

References:

1. Zhang, L-H, Wang, Z, Fan, Q-Q, Mao, Y, Hua, D. . AK5, a novel prognosis marker, inhibits apoptosis and promotes autophagy as well as proliferation in human gastric cancer. In European review for medical and pharmacological sciences, 23, 9900-9906. doi:10.26355/eurrev_201911_19555. https://pubmed.ncbi.nlm.nih.gov/31799658/

2. Muñiz-Castrillo, Sergio, Hedou, Julien Jacques, Ambati, Aditya, Mignot, Emmanuel, Honnorat, Jérôme. . Distinctive clinical presentation and pathogenic specificities of anti-AK5 encephalitis. In Brain : a journal of neurology, 144, 2709-2721. doi:10.1093/brain/awab153. https://pubmed.ncbi.nlm.nih.gov/33843981/

3. Yang, Shiyun, Chen, Bolun, Zhang, Jiatong, Chen, Jibing, Luo, Ning. 2025. Single-cell sequencing reveals that AK5 inhibits apoptosis in AD oligodendrocytes by regulating the AMPK signaling pathway. In Molecular biology reports, 52, 213. doi:10.1007/s11033-025-10311-x. https://pubmed.ncbi.nlm.nih.gov/39921763/

4. Ahn, Bokyung, Chae, Yang Seok, Lee, Soo Kyung, Moon, Ji Wook, Park, Sun-Hwa. 2021. Identification of novel DNA hypermethylation of the adenylate kinase 5 promoter in colorectal adenocarcinoma. In Scientific reports, 11, 12626. doi:10.1038/s41598-021-92147-6. https://pubmed.ncbi.nlm.nih.gov/34135408/

5. Siddiqui, M Sarim, Shahi, Mehdi H, Castresana, Javier S. 2024. The role of the adenylate kinase 5 gene in various diseases and cancer. In Journal of clinical and translational science, 8, e96. doi:10.1017/cts.2024.536. https://pubmed.ncbi.nlm.nih.gov/39655021/