CLU, also known as clusterin and apolipoprotein J (apoJ), is a highly evolutionary conserved glycoprotein. It functions as a molecular chaperone, being one of the most important extracellular chaperones. CLU is involved in multiple physiological and pathophysiological functions, exerting a cytoprotective role [2]. It participates in various processes such as programmed cell death, metastasis, invasion, proliferation, and cell growth by regulating diverse signaling pathways in cancer, and also in processes like lipid transport, suppression of the complement system in the context of Alzheimer's disease (AD) [3,4].

In oral cancer, CLU localizes to mitochondria and acts as an adaptor protein to induce mitophagy, controlling mitochondrial damage. It coordinates with BAX and LC3 to recruit autophagic machinery around damaged mitochondria in response to cisplatin treatment, and triggers class III phosphatidylinositol 3-kinase (PtdIns3K) activity. Additionally, CLU promotes mitophagic degradation of MSX2 through an AKT-DNM1L/Drp1 axis to maintain SOX2-mediated stemness in oral cancer stem cells [1,5]. In Alzheimer's disease, its expression is increased, and it is involved in processes like aggregation and clearance of amyloid-beta (Aβ), neuroinflammation, lipid metabolism, etc. [4].

In conclusion, CLU has diverse essential biological functions. In oral cancer, it plays a role in mitophagy and maintaining cancer stem cell properties, while in Alzheimer's disease, it is involved in multiple pathogenic processes. These functions are revealed through studies which likely include in-vivo models, though specific KO/CKO mouse model details were not provided in the references. Understanding CLU can provide potential therapeutic strategies for oral cancer and Alzheimer's disease [1,4,5].

References:

1. Praharaj, Prakash P, Patra, Srimanta, Singh, Amruta, Chae, Han J, Bhutia, Sujit K. 2024. CLU (clusterin) and PPARGC1A/PGC1α coordinately control mitophagy and mitochondrial biogenesis for oral cancer cell survival. In Autophagy, 20, 1359-1382. doi:10.1080/15548627.2024.2309904. https://pubmed.ncbi.nlm.nih.gov/38447939/

2. Rohne, Philipp, Prochnow, Hans, Koch-Brandt, Claudia. . The CLU-files: disentanglement of a mystery. In Biomolecular concepts, 7, 1-15. doi:10.1515/bmc-2015-0026. https://pubmed.ncbi.nlm.nih.gov/26673020/

3. Zhang, Yefei, Lv, Xiang, Chen, Liming, Liu, Yan. 2022. The role and function of CLU in cancer biology and therapy. In Clinical and experimental medicine, 23, 1375-1391. doi:10.1007/s10238-022-00885-2. https://pubmed.ncbi.nlm.nih.gov/36098834/

4. Uddin, Md Sahab, Kabir, Md Tanvir, Begum, Mst Marium, Behl, Tapan, Ashraf, Ghulam Md. 2020. Exploring the Role of CLU in the Pathogenesis of Alzheimer's Disease. In Neurotoxicity research, 39, 2108-2119. doi:10.1007/s12640-020-00271-4. https://pubmed.ncbi.nlm.nih.gov/32820456/

5. Praharaj, Prakash P, Patra, Srimanta, Mishra, Soumya R, Patil, Shankargouda, Bhutia, Sujit K. 2023. CLU (clusterin) promotes mitophagic degradation of MSX2 through an AKT-DNM1L/Drp1 axis to maintain SOX2-mediated stemness in oral cancer stem cells. In Autophagy, 19, 2196-2216. doi:10.1080/15548627.2023.2178876. https://pubmed.ncbi.nlm.nih.gov/36779631/