中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (2): 189-192.doi: 10.4103/1673-5374.244782

• 综述:退行性病与再生 •    下一篇

作为突触的肌萎缩性侧索硬化

  

  • 出版日期:2019-02-15 发布日期:2019-02-15

Amyotrophic lateral sclerosis as a synaptopathy

Matthew J. Fogarty 1, 2   

  1. 1 Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA
    2 School of Biomedical Sciences, The University of Queensland, St. Lucia, Australia
  • Online:2019-02-15 Published:2019-02-15
  • Contact: Matthew J. Fogarty, PhD, fogarty.matthew@mayo.edu.
  • Supported by:

     The author is the recipient of an NHMRC CJ Martin Early Career Fellowship

摘要:

orcid:0000-0002-5140-6612(Matthew J. Fogarty)

Abstract:

The synapse is an incredibly specialized structure that allows for the coordinated communication of information from one neuron to another. When assembled into circuits, steady streams of excitatory and inhibitory synaptic activity shape neural outputs. At the organismal level, ensembles of neural networks underlie behavior, emotion and memory. Disorder or dysfunctions of synapses, a synaptopathy, may underlie a host of developmental and degenerative neurological conditions. There is a possibility that amyotrophic lateral sclerosis may be a result of a synaptopathy within the neuromotor system. To this end, particular attention has been trained on the excitatory glutamatergic synapses and their morphological proxy, the dendritic spine. The extensive detailing of these dysfunctions in vulnerable neuronal populations, including corticospinal neurons and motor neurons, has recently been the subject of original research in rodents and humans. If amyotrophic lateral sclerosis is indeed a synaptopathy, it is entirely consistent with other proposed pathogenic mechanisms – including glutamate excitotoxicity, accumulation of misfolded proteins and mitochondrial dysfunction at distal axon terminals (cortico-motor neuron and neuromuscular). Further, although the exact mechanism of disease spread from region to region is unknown, the synaptopathy hypothesis is consistent with emerging die-forward evidence and the prion-like propagation of misfolded protein aggregates to distant neuronal populations. Here in this mini-review, we focus on the timeline of synaptic observations in both cortical and spinal neurons from different rodent models, and provide a conceptual framework for assessing the synaptopathy hypothesis in amyotrophic lateral sclerosis.

Key words: motor neuron, motor cortex, corticospinal, excitotoxicity, synaptic transmission, dendrites, dendritic spines, neuromuscular junction