Anti-dementia drugs for Alzheimer disease in present and future

Toshitaka Nabeshima, Yukihiro Noda, Hiroyuki Kamei

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalFolia Pharmacologica Japonica
Volume120
Issue numberSUPPL. 1
Publication statusPublished - 17-12-2002
Externally publishedYes

Fingerprint

Dementia
Alzheimer Disease
tau Proteins
Galantamine
Acetylcholine
Tacrine
Pharmaceutical Preparations
Rivastigmine
Esterases
Cognition
Phosphorylation
Allosteric Site
Serum Amyloid A Protein
Amyloid Precursor Protein Secretases
Intermediate Filaments
Amyloid Plaques
Neuroprotective Agents
Cell- and Tissue-Based Therapy
N-Methyl-D-Aspartate Receptors
Nicotine

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Nabeshima, Toshitaka ; Noda, Yukihiro ; Kamei, Hiroyuki. / Anti-dementia drugs for Alzheimer disease in present and future. In: Folia Pharmacologica Japonica. 2002 ; Vol. 120, No. SUPPL. 1.
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Anti-dementia drugs for Alzheimer disease in present and future. / Nabeshima, Toshitaka; Noda, Yukihiro; Kamei, Hiroyuki.

In: Folia Pharmacologica Japonica, Vol. 120, No. SUPPL. 1, 17.12.2002.

Research output: Contribution to journalArticle

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