|
 |
|
|
| Subject Categories: Neuroscience | Molecular Biology of Disease |
|
| The EMBO Journal
(2007) 26, 2755–2767, doi:10.1038/sj.emboj.7601707 Published online 3 May 2007 |
|
| Transgenic mice overexpressing reticulon 3 develop neuritic abnormalities |
|
|
| Xiangyou Hu1, 4, Qi Shi1, 4, Xiangdong Zhou1, Wanxia He1, Hong Yi2, Xinghua Yin1, Marla Gearing3, Allan Levey3 and Riqiang Yan1 |
|
|
1 Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH, USA 2 Microscopy Core, Emory University School of Medicine, Atlanta, GA, USA 3 Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA To whom correspondence should be addressed Riqiang Yan, Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Tel.: +1 216 445 2690; Fax: +1 216 444 7927; E-mail: yanr@ccf.org 4 These authors contributed equally to this work Received 24 November 2006; Accepted 23 March 2007; Published online 3 May 2007. |
|
|
|
| Abstract |
|
| Dystrophic neurites are swollen dendrites or axons recognizable near amyloid plaques as a part of important pathological feature of Alzheimer's disease (AD). We report herein that reticulon 3 (RTN3) is accumulated in a distinct population of dystrophic neurites named as RTN3 immunoreactive dystrophic neurites (RIDNs). The occurrence of RIDNs is concomitant with the formation of high-molecular-weight RTN3 aggregates in brains of AD cases and mice expressing mutant APP. Ultrastructural analysis confirms accumulation of RTN3-containing aggregates in RIDNs. It appears that the protein level of RTN3 governs the formation of RIDNs because transgenic mice expressing RTN3 will develop RIDNs, initially in the hippocampal CA1 region, and later in other hippocampal and cortical regions. Importantly, we show that the presence of dystrophic neurites in Tg-RTN3 mice causes impairments in spatial learning and memory, as well as synaptic plasticity, implying that RIDNs potentially contribute to AD cognitive dysfunction. Together, we demonstrate that aggregation of RTN3 contributes to AD pathogenesis by inducing neuritic dystrophy. Inhibition of RTN3 aggregation is likely a therapeutic approach for reducing neuritic dystrophy. |
|
| Keywords: BACE1, diffuse plaques, dystrophic neurites, Nogo, reticulon |
|
|
|
Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSNature News and Views (12 Dec 1991) A welcoming environment for amyloid plaques Nature Neuroscience News and Views (01 Apr 2003) RESEARCHTransgenic mice overexpressing reticulon 3 develop neuritic abnormalities The EMBO Journal Article Reticulon family members modulate BACE1 activity and amyloid-β peptide generation Nature Medicine Article (01 Sep 2004) |
|
|
| |
| |
| |
 | Email link to a friend |
| |
 | Download PDF |
| |
 | Full text |
| |
| |
| |
 | Next article |
| |
 | Previous article |
| |
 | Table of contents |
| |
| |
 | Rights and permissions |
| |
 | Reprints |
| |
| |
| |
 Register for table of contents by email | |
| |
| |
| |
