Anti-dementia drugs for Alzheimer disease in present and future

Toshitama Nabeshima, Yukihiro Noda, Hiroyuki Kamei

研究成果: Article査読

4 被引用数 (Scopus)


Alzheimer disease(AD) is characterized as neurodegenerative disease showing impairment of cognitive function, death of neuronal cells, numerous numbers of senile plaques and tangle of neurofilaments. There are two different hypotheses that neurotoxicity of aggregated amyloid β protein(A β) and hyperphosphorylation of tau protein are the causes of AD. The dysfunction of cholinergic neuronal system is observed in the early stage of AD. Therefore, the strategy to increase of acetylcholine (ACh) level in brain by using ACh esterase inhibitor is mainstream in the present. We have tacrine, donepezil, rivastigmine and galantamine. Tacrine, the first drug for AD, is replaced by other drugs, because of its hepatic toxicity. Galantamine binds allosteric sites of nicotine receptor and stimulates it in addition to its inhibitory effect on ACh esterase. Metamantine was approved in EU in 2002. It is non-competitive inhibitor of NMDA receptors, and dopamine releaser, which has neuroprotective effect. All of the above drugs improve cognitive function of patients, and they could delay hospitalization for 7 months or more. In the present anti-inflammatory drugs, anti-oxidative drugs and estrogen are under investigation. As anti-A β therapy, inhibitors of β -and γ-secretase, A β aggregation inhibitors, A β degradation stimulators and A β vaccination are possible strategies. The inhibitors of tau protein phosphorylation and activators of phosphates could be that of anti-tau protein phosphorylation. Additionally, it is expected to have the strategies such as neuroregeneration by neurotorophic factors and immunopyline ligands, and supply of neuronal cells by gene therapy and human ES cells.

ジャーナルFolia Pharmacologica Japonica
出版ステータスPublished - 17-12-2002

All Science Journal Classification (ASJC) codes

  • Pharmacology

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