中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (2): 333-334.doi: 10.4103/1673-5374.343903

• 观点:退行性病与再生 • 上一篇    下一篇

多奈哌齐-石杉碱杂种与合成膜模型的相互作用

  

  • 出版日期:2023-02-15 发布日期:2022-08-06

On the interaction of a donepezil-huprine hybrid with synthetic membrane models

Pablo Zambrano*   

  1. Max Planck Institute of Biochemistry, Cellular and Molecular Biophysics, Munich, Germany
  • Online:2023-02-15 Published:2022-08-06
  • Contact: Pablo Zambrano, PhD, zambranolobos@biochem.mpg.de.

摘要: https://orcid.org/0000-0001-5499-6091 (Pablo Zambrano)

Abstract: Alzheimer’s disease is the most prevalent type of dementia today, discovered and described by Alois Alzheimer in 1907. According to the World Alzheimer Report 2021, 75% of people with dementia worldwide are undiagnosed, equivalent to 41 million people (Gauthier et al., 2021). With each passing year, the number of people affected by these diseases is increasing, and the estimates of suffering from them in the future are growing. There are currently only four drugs used against Alzheimer’s disease: donepezil, rivastigmine, galantamine, and memantine. The first three, based on the cholinergic hypothesis, aim to inhibit the acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) to prevent the reduction of acetylcholine levels in the brain. Memantine, on the other hand, is based on the glutamatergic hypothesis, according to which in Alzheimer’s disease there are higher than normal levels of glutamate which, through interaction with the glutamatergic N-methyl-D-aspartate receptor, lead to abnormally high levels of calcium which cause neuronal damage. Blocking N-methyl-D-aspartate receptors to reduce these calcium levels is a therapeutic target to control this disease, and this is the mechanism of action of memantine (Rubin, 2021). Recently, the drug Aducanumab has also been approved in the United States. This is a human IgG1 monoclonal antibody that primarily binds to amyloid-beta (Aβ) aggregates, soluble oligomers, and also insoluble fibrils, limiting the toxicity of these species.