Orally active NGF synthesis stimulators: Potential therapeutic agents in Alzheimer's disease

Kiyofumi Yamada, Atsumi Nitta, Takaaki Hasegawa, Kazuyuki Fuji, Masayuki Hiramatsu, Tsutomu Kameyama, Yoshiko Furukawa, Kyozo Hayashi, Toshitaka Nabeshima

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

The degeneration of cholinergic neurons may be responsible for cognitive impairment in patients with Alzheimer's disease (AD). Since nerve growth factor (NGF) plays an important role in the survival and maintenance of cholinergic neurons in the central nervous system, this factor may have some beneficial effects on the cognitive impairment observed in patients with AD. However, since NGF does not cross the blood-brain barrier and is easily metabolized when administered peripherally, if can only be used when directly injected into the brain. In this review, we show that repeated oral administration of the NGF synthesis stimulators, idebenone and propentofylline, partially restored the age-associated decrease of NGF in the frontal and parietal cortices. Furthermore, this treatment attenuated the impairment of performance in the water maze, passive avoidance, and habituation tasks in rats with bilateral forebrain lesions, and in rats which had received continuous infusion of anti-NGF antibody into the septum. The behavioral improvement induced by idebenone and propentofylline was accompanied by recovery of both the reduced activity of choline acetyltransferase and the changes in [3H] QNB binding. These results suggest that the use of NGF synthesis stimulators may provide a novel therapeutic approach to cholinergic dysfunction.

Original languageEnglish
Pages (from-to)117-122
Number of pages6
JournalBehavioural Brain Research
Volume83
Issue number1-2
DOIs
Publication statusPublished - 02-1997
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

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    Yamada, K., Nitta, A., Hasegawa, T., Fuji, K., Hiramatsu, M., Kameyama, T., Furukawa, Y., Hayashi, K., & Nabeshima, T. (1997). Orally active NGF synthesis stimulators: Potential therapeutic agents in Alzheimer's disease. Behavioural Brain Research, 83(1-2), 117-122. https://doi.org/10.1016/S0166-4328(97)86054-8