HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Faculty of Pharmaceutical Sciences >
Peer-reviewed Journal Articles, etc >

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

This item is licensed under: Creative Commons Attribution 2.0 Generic

Files in This Item:
MN7_50.pdf2.21 MBPDFView/Open
Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/51384

Title: Hyperpolarization-activated cyclic nucleotide gated channels: a potential molecular link between epileptic seizures and Aβ generation in Alzheimer's disease
Authors: Saito, Yuhki Browse this author →KAKEN DB
Inoue, Tsuyoshi Browse this author
Zhu, Gang Browse this author
Kimura, Naoki Browse this author
Okada, Motohiro Browse this author
Nishimura, Masaki Browse this author
Kimura, Nobuyuki Browse this author
Murayama, Shigeo Browse this author
Kaneko, Sunao Browse this author
Shigemoto, Ryuichi Browse this author
Imoto, Keiji Browse this author
Suzuki, Toshiharu Browse this author →KAKEN DB
Issue Date: 3-Oct-2012
Publisher: BioMed Central
Journal Title: Molecular Neurodegeneration
Volume: 7
Start Page: 50
Publisher DOI: 10.1186/1750-1326-7-50
Abstract: 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.
Rights: http://creativecommons.org/licenses/by/2.0/
Type: article
URI: http://hdl.handle.net/2115/51384
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 鈴木 利治

Export metadata:

OAI-PMH ( junii2 , jpcoar_1.0 )

MathJax is now OFF:


 

 - Hokkaido University