Axonal transport defects in neurodegenerative diseases.
Axonal transport defects in neurodegenerative diseases.
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DOI：
10.1523/jneurosci.3463-09.2009
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发表时间：
2009-10-14
期刊：
影响因子：
--
通讯作者：
Brady ST
中科院分区：
文献类型：
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作者：
Morfini GA;Burns M;Binder LI;Kanaan NM;LaPointe N;Bosco DA;Brown RH Jr;Brown H;Tiwari A;Hayward L;Edgar J;Nave KA;Garberrn J;Atagi Y;Song Y;Pigino G;Brady ST
成人发作性神经退行性疾病（AOND）包括一组异质性神经系统疾病，其特征在于神经元功能的进行性、年龄依赖性下降和选定神经元群体的丧失。突触功能和轴突连接的改变代表AOND的早期和关键的致病事件，但这些缺陷的分子机制仍然难以捉摸。神经元的大尺寸和复杂的亚细胞结构使它们特别容易受到轴突运输（AT）改变的影响。因此，在大多数AOND中已经记录了AT的缺陷，表明通过不同的致病途径获得的常见缺陷。这些观察结果表明，许多AOND可归类为铁代谢异常，即AT改变是发病机制中的关键组成部分的疾病。这里的主题涉及几种AOND中AT改变的各种分子机制。这些机制的照明提供了一个框架，旨在防止轴突和突触功能障碍的几个主要AOND的新的治疗策略的发展。
Adult-onset neurodegenerative diseases (AONDs) comprise a heterogeneous group of neurological disorders characterized by a progressive, age-dependent decline in neuronal function and loss of selected neuronal populations. Alterations in synaptic function and axonal connectivity represent early and critical pathogenic events in AONDs, but molecular mechanisms underlying these defects remain elusive. The large size and complex subcellular architecture of neurons render them uniquely vulnerable to alterations in axonal transport (AT). Accordingly, deficits in AT have been documented in most AONDs, suggesting a common defect acquired through different pathogenic pathways. These observations suggest that many AONDs can be categorized as dysferopathies, diseases where alterations in AT represent a critical component in pathogenesis. Topics here address various molecular mechanisms underlying alterations in AT in several AONDs. Illumination of such mechanisms provides a framework for the development of novel therapeutic strategies aimed to prevent axonal and synaptic dysfunction in several major AONDs.