Hyperpolarization-activated cyclic nucleotide gated channels: a potential molecular link between epileptic seizures and Aβ generation in Alzheimer's disease

Saito, Yuhki; Inoue, Tsuyoshi; Zhu, Gang; Kimura, Naoki; Okada, Motohiro; Nishimura, Masaki; Kimura, Nobuyuki; Murayama, Shigeo; Kaneko, Sunao; Shigemoto, Ryuichi; Imoto, Keiji; Suzuki, Toshiharu

Hyperpolarization-activated cyclic nucleotide gated channels: a potential molecular link between epileptic seizures and Aβ generation in Alzheimer's disease

Saito, Yuhki; Inoue, Tsuyoshi; Zhu, Gang et al.

Molecular Neurodegeneration, 2012, 7, 50

Permalink : https://hdl.handle.net/2115/51384

このアイテムのアクセス数:973件（2026-08-12 08:51 集計）

閲覧可能ファイル

ファイル	フォーマット	サイズ	閲覧回数	説明
MN7_50	pdf	2.15 MB	888

論文情報

ファイル出力 EndNote Basic出力 Mendeley出力

アクセス権	open access
URI	https://hdl.handle.net/2115/51384
タイトル	Hyperpolarization-activated cyclic nucleotide gated channels: a potential molecular link between epileptic seizures and Aβ generation in Alzheimer's disease
著者	Saito, Yuhki ; Inoue, Tsuyoshi ; Zhu, Gang ; Kimura, Naoki ; Okada, Motohiro ; Nishimura, Masaki ; Kimura, Nobuyuki ; Murayama, Shigeo ; Kaneko, Sunao ; Shigemoto, Ryuichi ; Imoto, Keiji ; Suzuki, Toshiharu
e-Rad_Researcher 70548180 著者名 Saito, Yuhki
著者名 Inoue, Tsuyoshi
著者名 Zhu, Gang
著者名 Kimura, Naoki
著者名 Okada, Motohiro
著者名 Nishimura, Masaki
著者名 Kimura, Nobuyuki
著者名 Murayama, Shigeo
著者名 Kaneko, Sunao
著者名 Shigemoto, Ryuichi
著者名 Imoto, Keiji
e-Rad_Researcher 80179233 著者名 Suzuki, Toshiharu
言語	英語
発行日	2012-10-03
出版者	BioMed Central
収録物名	Molecular Neurodegeneration
巻(号)	7
ページ	50
抄録	Background: One of the best-characterized causative factors of Alzheimer's disease (AD) is the generation of amyloid-β peptide (Aβ). AD subjects are at high risk of epileptic seizures accompanied by aberrant neuronal excitability, which in itself enhances Aβ generation. However, the molecular linkage between epileptic seizures and Aβ generation in AD remains unclear. Results: X11 and X11-like (X11L) gene knockout mice suffered from epileptic seizures, along with a malfunction of hyperpolarization-activated cyclic nucleotide gated (HCN) channels. Genetic ablation of HCN1 in mice and HCN1 channel blockage in cultured Neuro2a (N2a) cells enhanced Aβ generation. Interestingly, HCN1 levels dramatically decreased in the temporal lobe of cynomolgus monkeys (Macaca fascicularis) during aging and were significantly diminished in the temporal lobe of sporadic AD patients. Conclusion: Because HCN1 associates with amyloid-β precursor protein (APP) and X11/X11L in the brain, genetic deficiency of X11/X11L may induce aberrant HCN1 distribution along with epilepsy. Moreover, the reduction in HCN1 levels in aged primates may contribute to augmented Aβ generation. Taken together, HCN1 is proposed to play an important role in the molecular linkage between epileptic seizures and Aβ generation, and in the aggravation of sporadic AD.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 2.0 Generic
PISSN	1750-1326
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1186/1750-1326-7-50