YAP: A Turning Point for Cognitive Function in AD
DOI:
https://doi.org/10.47611/jsrhs.v14i1.9043Keywords:
Alzheimer's Disease, Yes-Associated Protein, Hippocampus, Astrocytes, Astrocytic SenescenceAbstract
Alzheimer’s Disease (AD) is a debilitating neurological condition often associated with gradual cognitive decline and memory impairment. A manner in which Alzheimer’s presents itself is by impeding the astrocytic function caused by tau aggregates and amyloid beta plaques, which are thought to play a part in the pathogenesis of AD, leading to dysregulation of neurogenesis. The brain becomes incapable of developing new neurons leading to progressive neuronal loss and cognitive deterioration typical of Alzheimer’s disease. However, recent studies have identified Yap as a promising target for new drugs. The development of many organs depends on a transcriptional cofactor known as Yes-associated protein (YAP), which is essential for the normal functioning Hippo pathway. However, its functions concerning brain development remain largely obscure. Furthermore, YAP has been seen to curb astrocytic senescence thereby enhancing neurogenesis required for combating the cognitive disorders accompanying hostile neuronal milieu common with AD. This paper examines one such study conducted wherein YAP was introduced to WT and AD mice and the results are then analyzed through rodent field tests. The results verified the claim that YAP can help curb Astrocytic Senescence and therefore retain and even slightly improve cognitive function. However, it is crucial to note that YAP has potential side effects. Side effects including tumor progression and cell proliferation are observed with YAP-inducing treatments since YAP is also a key player in organ growth and regeneration. Further study is crucial to solidify the position of YAP as a treatment for AD.
Downloads
References or Bibliography
Alzheimer’s Disease Fact Sheet | National Institute on Aging, www.nia.nih.gov/health/alzheimers-and-dementia/alzheimers-disease-fact-sheet. (n.d.).
Bhat, R., Crowe, E. P., Bitto, A., Moh, M., Katsetos, C. D., Garcia, F. U., … Torres, C. (2012). Astrocyte senescence as a component of Alzheimer’s disease. PloS One, 7(9), e45069. doi:10.1371/journal.pone.0045069
Cassé, F., Richetin, K., & Toni, N. (2018). Astrocytes’ contribution to adult neurogenesis in physiology and Alzheimer’s disease. Frontiers in Cellular Neuroscience, 12. doi:10.3389/fncel.2018.00432
Childs, B. G., Durik, M., Baker, D. J., & van Deursen, J. M. (2015). Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nature Medicine, 21(12), 1424–1435. doi:10.1038/nm.4000
Choi, S. (2018). Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model. ” Science. Science, 361. doi:10.1126/science.aan8821
Csipo, T., Lipecz, A., Ashpole, N. M., Balasubramanian, P., & Tarantini, S. (2020). Astrocyte senescence contributes to cognitive decline. GeroScience, 42(1), 51–55. doi:10.1007/s11357-019-00140-9
Dhana, K., Evans, D. A., Rajan, K. B., Bennett, D. A., & Morris, M. C. (2020). Healthy lifestyle and the risk of Alzheimer dementia: Findings from 2 longitudinal studies. Neurology, 95(4), e374–e383. doi:10.1212/WNL.0000000000009816
Fan, W., Jurado-Arjona, J., Alanis-Lobato, G., Péron, S., Berger, C., Andrade-Navarro, M. A., … Berninger, B. (2023). The transcriptional co‐activator Yap1 promotes adult hippocampal neural stem cell activation. The EMBO Journal, 42(11). doi:10.15252/embj.2021110384
Griffiths, B. B., Bhutani, A., & Stary, C. M. (2020). Adult neurogenesis from reprogrammed astrocytes. Neural Regeneration Research, 15(6), 973–979. doi:10.4103/1673-5374.270292
Han, X., Zhang, T., Liu, H., Mi, Y., & Gou, X. (2020). Astrocyte senescence and Alzheimer’s disease: A review. Frontiers in Aging Neuroscience, 12, 148. doi:10.3389/fnagi.2020.00148
Kumar, A., Pareek, V., Faiq, M. A., Ghosh, S. K., & Kumari, C. (2019). ADULT NEUROGENESIS IN HUMANS: A review of basic concepts, history, current research, and clinical implications. Innovations in Clinical Neuroscience, 16(5–6), 30–37. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/31440399
Lim, D. A., & Alvarez-Buylla, A. (1999). Interaction between astrocytes and adult subventricular zone precursors stimulates neurogenesis. Proceedings of the National Academy of Sciences of the United States of America, 96(13), 7526–7531. doi:10.1073/pnas.96.13.7526
Mahdi, N., & Bagheri-Mohammadi, S. (2021). Adult Hippocampal Neurogenesis and Alzheimer’s Disease: Novel Application of Mesenchymal Stem Cells and Their Role in Hippocampal Neurogenesis. International Journal of Molecular and Cellular Medicine.
Meng, Q., Lin, M.-S., & Tzeng, I.-S. (2020). Relationship between exercise and Alzheimer’s disease: A narrative literature review. Frontiers in Neuroscience, 14, 131. doi:10.3389/fnins.2020.00131
Mitchell, E. (2020). XMU-MP-1 induces growth arrest in a model human mini-organ and antagonizes cell cycle-dependent paclitaxel cytotoxicity. Cell Division, 15. doi:10.1186/s13008-020-00067-0
Rees, V. (2020). Yap Protein Identified as New Target for Alzheimer’s Disease.” Drug Target Review, Drug Target Review. In protein-identified-as-new-target-for-alzheimers-disease/#:~:text=YAP positively affects the activity.
Shega, J. W., Ellner, L., Lau, D. T., & Maxwell, T. L. (2009). Cholinesterase inhibitor and N-methyl-D-aspartic acid receptor antagonist use in older adults with end-stage dementia: a survey of hospice medical directors. Journal of Palliative Medicine, 12(9), 779–783. doi:10.1089/jpm.2009.0059
Spector, A., Woods, B., & Orrell, M. (2008). Cognitive stimulation for the treatment of Alzheimer’s disease. Expert Review of Neurotherapeutics, 8(5), 751–757. doi:10.1586/14737175.8.5.751
Sung, P.-S., Lin, P.-Y., Liu, C.-H., Su, H.-C., & Tsai, K.-J. (2020). Neuroinflammation and neurogenesis in Alzheimer’s disease and potential therapeutic approaches. International Journal of Molecular Sciences, 21(3), 701. doi:10.3390/ijms21030701
Verkhratsky, A., Olabarria, M., Noristani, H. N., Yeh, C.-Y., & Rodriguez, J. J. (2010). Astrocytes in Alzheimer’s disease. Neurotherapeutics: The Journal of the American Society for Experimental NeuroTherapeutics, 7(4), 399–412. doi:10.1016/j.nurt.2010.05.017
Wei, D. C., & Histology, A. (2023). #:~:text=Astrocytes are a subtype of,barrier, and promoting synapse formation.
Xie, Q., Chen, J., Feng, H., Peng, S., Adams, U., Bai, Y., … Yuan, Z. (2013). YAP/TEAD-mediated transcription controls cellular senescence. Cancer Research, 73(12), 3615–3624. doi:10.1158/0008-5472.CAN-12-3793
Xu, X., Shen, X., Wang, J., Feng, W., Wang, M., Miao, X., … Huang, Z. (2021). YAP prevents premature senescence of astrocytes and cognitive decline of Alzheimer’s disease through regulating CDK6 signaling. Aging Cell, 20(9). doi:10.1111/acel.13465
Xu, X., Wang, Y., & Huang, Z. (2022). YAP: a novel target for Alzheimer’s disease. Aging, 14(9), 3724–3725. doi:10.18632/aging.204045
Xu, X., Shen, X., Feng, W., Yang, D., Jin, L., Wang, J., … Huang, Z. (2020). D-galactose induces senescence of glioblastoma cells through YAP-CDK6 pathway. Aging, 12(18), 18501–18521. doi:10.18632/aging.103819
Published
How to Cite
Issue
Section
Copyright (c) 2025 Tejasvi Kondury; Dr. Jobin Varkey, Jothsna Kethar
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Copyright holder(s) granted JSR a perpetual, non-exclusive license to distriute & display this article.
