中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (10): 1553-1556.doi: 10.4103/1673-5374.193224

• 综述:退行性病与再生 • 上一篇    下一篇

神经生长因子通路异常可否揭开阿尔茨海默病的“序幕”?

  

  • 收稿日期:2016-09-28 出版日期:2016-10-31 发布日期:2016-10-31
  • 基金资助:
    这项研究由教育、大学和研究部(MIUR / FIRB)资助PC

Impairment of the nerve growth factor pathway driving amyloid accumulation in cholinergic neurons: the incipit of the Alzheimer’s disease story?

Viviana Triaca*, Pietro Calissan   

  1. European Brain Research Institute (EBRI)/R.L. Montalcini Foundation, and Institute of Cell Biology and Neuroscience, National Research Council (IBCN-CNR), Rome, Italy
  • Received:2016-09-28 Online:2016-10-31 Published:2016-10-31
  • Contact: Viviana Triaca, Ph.D., viviana.triaca@ibcn.cnr.it.
  • Supported by:
    This study was supported by Ministry of Education, Universities and Research (MIUR/FIRB) funding to PC.

摘要: 如今,大量研究报道或许会开启一个新场景:神经生长因子信号转导障碍是阿尔茨海默病的病征,并可能解释APP介导的前脑突触障碍。最近关于阿尔茨海默病解剖特性的研究表明了阿尔茨海默病症状前期的功能和分子轮廓,以最大化实现现有治疗方法的疗效和设置新的靶向治疗。 事实上,神经生长因子激活基底前脑胆碱能神经元代谢的一个关键是神经营养因子通路,这是阿尔茨海默病中的第一个自我平衡系统。神经生长因子信号传导功能障碍一直被认为在阿尔茨海默病后期出现,可造成淀粉样蛋白驱使的脑胆碱能神经元神经营养因子逆行,轴突转运损坏的结果。 综上所述,隔-海马胆碱能系统中阐述神经生长因子调控APP代谢分子事件的基本机制具有临床转化价值,以减缓并最终阻止轻度认知障碍和对阿尔茨海默病进展的作用。

Abstract: The current idea behind brain pathology is that disease is initiated by mild disturbances of common physiological processes. Overtime, the disruption of the neuronal homeostasis will determine irreversible degeneration and neuronal apoptosis. Tis could be also true in the case of nerve growth factor (NGF) alterations in sporadic Alzheimer’s disease (AD), an age-related pathology characterized by cholinergic loss, amyloid plaques and neurofibrillary tangles. In fact, the pathway activated by NGF, a key neurotrophin for the metabolism of basal forebrain cholinergic neurons (BFCN), is one of the frst homeostatic systems a?ected in prodromal AD. NGF signaling dysfunctions have been thought for decades to occur in AD late stages, as a mere consequence of amyloid-driven disruption of the retrograde axonal transport of neurotrophins to BFCN. Nowadays, a wealth of knowledge is potentially opening a new scenario: NGF signaling impairment occurs at the onset of AD and correlates better than amyloid load with cognitive decline. Te recent acceleration in the characterization of anatomical, functional and molecular profles of early AD is aimed at maximizing the efficacy of existing treatments and setting novel therapies. Accordingly, the elucidation of the molecular events underlying APP metabolism regulation by the NGF pathway in the septo-hippocampal system is crucial for the identifcation of new target molecules to slow and eventually halt mild cognitive impairment (MCI) and its progression toward AD.

Key words: Alzheimer’s disease onset, NGF pathway disturbances, intraneuronal amyloid generation and release, basal forebrain cholinergic neurons