Research progress on the targets and therapies of Alzheimer’s disease
DOI:
https://doi.org/10.54097/b4jvw792Keywords:
Alzheimer’s disease, target, therapy.Abstract
Alzheimer 's disease (AD) is a progressive neurodegenerative disease. Most of the patients have the following characteristics, such as abnormalities in memory, language, and behavioral ability. It is very common in dementia in the elderly. The pathological features are mainly the plaques formed by Aβ protein deposition and the neurofibrillary tangles. The causes of AD are complex, and there are many pathological hypotheses. The current clinical therapeutic drugs for AD are mainly cholinesterase inhibitors developed based on the cholinergic hypothesis and receptor antagonists targeting NMDA receptors. Although there are some research results on the targets based on other hypotheses, further research is needed for clinical application. Nevertheless, in recent years, there have been many new development directions, such as combination therapy. Multi-target combination therapy is expected to achieve better efficacy than traditional single-target therapy. This makes it even more important to develop drugs with different potential targets. This article introduces three current mainstream therapeutic targets and theories, and introduces the drugs based on them. At the same time, we also introduced 3 targets and therapies with good potential in the future, and introduced some current stage results and current drugs based on their research and development.
Downloads
References
Wu Dirong, ' Design, Synthesis and Activity Study of Scutellarin and Its Aglycone Derivatives for Alzheimer 's Disease Based on Multiple Mechanisms of Action, ' Master, Guizhou Medical University, 2022. doi: 10.27045/d.cnki.ggyyc.2022.000040.
A. Nandi et al., “Global and regional projections of the economic burden of Alzheimer’s disease and related dementias from 2019 to 2050: A value of statistical life approach,” eClinicalMedicine, vol. 51, p. 101580, Sep. 2022, doi: 10.1016/j.eclinm.2022.101580.
Du Rongrong, Qu Lianyue, Sun Shanshan, and Lin Jianyang, ' Research Status of Drug Therapy for Alzheimer 's Disease, ' Chinese Journal of Clinical Pharmacology, vol. 35, no. 5, pp. 489–492, 2019, doi: 10.13699/j.cnki.1001-6821.2019.05.024.
Li and Zhang, ' Pathogenesis Analysis of Alzheimer 's Disease, ' World 's Latest Medical Information Abstract, vol. 19, no. 44, pp. 27–28, 2019, doi: 10.19613/j.cnki.1671-3141.2019.44.014.
Wu, ' Effects of fluoxetine on behavior and hippocampal cholinergic neurons in early APP / PS1 transgenic AD mice, ' Master, Chongqing Medical University, 2019. Accessed: Jul. 16, 2023. [Online]. Available: https://kns.cnki.net/kcms2/article/abstract?v=3uoqIhG8C475KOm_zrgu4lQARvep2SAkOsSuGHvNoCRcTRpJSuXuqe3xhRj2a6nqqmbhtIaqASS-jIUZF54tJ4n0VdqYPLnK&uniplatform=NZKPT
Dai Tingting and Tian Shaowen, ' Advances in targeted therapy for Alzheimer 's disease, ' Journal of Central South Medical Sciences, vol. 43, no. 4, pp. 452–456, 2015, doi: 10.15972/j.cnki.43-1509/r.2015.04.026.
Li Wei, Liu Qiang, Huang Huiling, and Ma Aixia, ' Systematic Review of Lisdeming Capsule in the Treatment of Alzheimer 's Disease, ' Modern Commercial Industry, vol. 37, no. 12, pp. 86–89, 2016, doi: 10.19311/j.cnki.1672-3198.2016.12.042.
Yang Nanzhu, Yun Xianghua, Zhou Yuying, Wang Hongyan, and Wu Yuqiu, ' Systematic Review of Donepezil in the Treatment of Alzheimer 's Disease, ' Chinese Journal of Geriatric Cardiovascular and Cerebrovascular Disease, vol. 17, no. 1, pp. 61–66, 2015.
S. Ghosh, R. Ali, and S. Verma, “Aβ-oligomers: A potential therapeutic target for Alzheimer’s disease,” Int. J. Biol. Macromol., vol. 239, p. 124231, Jun. 2023, doi: 10.1016/j.ijbiomac.2023.124231.
A. Anand, A. A. Patience, N. Sharma, and N. Khurana, “The present and future of pharmacotherapy of Alzheimer’s disease: A comprehensive review,” Eur. J. Pharmacol., vol. 815, pp. 364–375, Nov. 2017, doi: 10.1016/j.ejphar.2017.09.043.
R. Malinow, “New developments on the role of NMDA receptors in Alzheimer’s disease,” Curr. Opin. Neurobiol., vol. 22, no. 3, pp. 559–563, Jun. 2012, doi: 10.1016/j.conb.2011.09.001.
X. Du, X. Wang, and M. Geng, “Alzheimer’s disease hypothesis and related therapies,” Transl. Neurodegener., vol. 7, no. 1, p. 2, Jan. 2018, doi: 10.1186/s40035-018-0107-y.
Y. Yang et al., “Intranasal insulin ameliorates tau hyperphosphorylation in a rat model of type 2 diabetes,” J. Alzheimers Dis. JAD, vol. 33, no. 2, pp. 329–338, 2013, doi: 10.3233/JAD-2012-121294.
A. Salminen, J. Ojala, K. Kaarniranta, M. Hiltunen, and H. Soininen, “Hsp90 regulates tau pathology through co-chaperone complexes in Alzheimer’s disease,” Prog. Neurobiol., vol. 93, no. 1, pp. 99–110, Jan. 2011, doi: 10.1016/j.pneurobio.2010.10.006.
Bi Danlei and Shen Yong, ' ApoE4 interferes with brain metabolism to induce Alzheimer 's disease, ' Technology Review, vol. 39, no. 20, pp. 92–100, 2021.
T.-P. V. Huynh et al., “Age-Dependent Effects of apoE Reduction Using Antisense Oligonucleotides in a Model of β-amyloidosis,” Neuron, vol. 96, no. 5, pp. 1013-1023.e4, Dec. 2017, doi: 10.1016/j.neuron.2017.11.014.
T. Islam et al., “Apolipoprotein E impairs amyloid-β fibril elongation and maturation,” FEBS J., vol. 287, no. 6, pp. 1208–1219, Mar. 2020, doi: 10.1111/febs.15075.
Q. Ma et al., “Blood-brain barrier-associated pericytes internalize and clear aggregated amyloid-β42 by LRP1-dependent apolipoprotein E isoform-specific mechanism,” Mol. Neurodegener., vol. 13, no. 1, p. 57, Oct. 2018, doi: 10.1186/s13024-018-0286-0.
J. B. Toledo et al., “CSF Apo-E levels associate with cognitive decline and MRI changes,” Acta Neuropathol. (Berl.), vol. 127, no. 5, pp. 621–632, May 2014, doi: 10.1007/s00401-013-1236-0.
J. M. Farfel, L. Yu, P. L. De Jager, J. A. Schneider, and D. A. Bennett, “Association of APOE with tau-tangle pathology with and without β-amyloid,” Neurobiol. Aging, vol. 37, pp. 19–25, Jan. 2016, doi: 10.1016/j.neurobiolaging.2015.09.011.
Huang, Xu, and Zhong, ' Barrier and Alzheimer 's Disease, ' Chinese Journal of Histochemistry and Cytochemistry, vol. 30, no. 2, pp. 189–194, 2021, doi: 10.16705/j.cnki.1004-1850.2021.02.013.
Xu Xinzi, Wang Junli, and Shao Wei, ' Prevention and treatment of Alzheimer 's disease based on collateral disease theory from the perspective of improving the function of neurovascular units, ' Journal of Anhui University of Traditional Chinese Medicine, vol. 42, no. 2, pp. 4–7, 2023.
J. L. Cummings, T. Morstorf, and K. Zhong, “Alzheimer’s disease drug-development pipeline: few candidates, frequent failures,” Alzheimers Res. Ther., vol. 6, no. 4, p. 37, Jul. 2014, doi: 10.1186/alzrt269.
Downloads
Published
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
