RTN/Nogo 在形成阿尔茨海默病神经纤维缠结中的作用。
RTN/Nogo in forming Alzheimer's neuritic plaques.
机构信息
Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
出版信息
Neurosci Biobehav Rev. 2010 Jul;34(8):1201-6. doi: 10.1016/j.neubiorev.2010.01.017. Epub 2010 Feb 6.
Abstract
One of the pathological hallmarks in brains of patients with Alzheimer's disease (AD) is the presence of neuritic plaques, in which amyloid deposits are surrounded by reactive gliosis and dystrophic neurites. Within neuritic plaques, reticulon 3 (RTN3), a homolog of Nogo protein, appears to regulate the formation of both amyloid deposition via negative modulation of BACE1 activity and dystrophic neurites via the formation of RTN3 aggregates. Transgenic mice over-expressing RTN3, but not the other known markers of dystrophic neurites in AD brain, spontaneously develop RTN3-immunoreactive dystrophic neurites. The presence of dystrophic neurites impairs cognition. Blocking abnormal RTN3 aggregation will increase the available RTN3 monomer and is therefore a promising therapeutic strategy for enhancing cognitive function in AD patients.
摘要
阿尔茨海默病（AD）患者大脑中的病理特征之一是存在神经纤维缠结，其中淀粉样沉积物被反应性神经胶质增生和退行性神经突所包围。在神经纤维缠结中，Reticulon 3（RTN3）是神经生长抑制因子蛋白的同源物，似乎通过负向调节 BACE1 活性来调节淀粉样沉积的形成，通过 RTN3 聚集来调节退行性神经突的形成。过表达 RTN3 的转基因小鼠会自发地产生 RTN3 免疫反应性退行性神经突，但不会产生 AD 脑中其他已知的退行性神经突标志物。退行性神经突的存在会损害认知。阻断异常 RTN3 聚集将增加可用的 RTN3 单体，因此是提高 AD 患者认知功能的有前途的治疗策略。
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