Axonal degeneration in Alzheimer's disease: when signaling abnormalities meet the axonal transport system.
Axonal degeneration in Alzheimer's disease: when signaling abnormalities meet the axonal transport system.
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DOI：
10.1016/j.expneurol.2012.06.003
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发表时间：
2013-08
影响因子：
5.3
通讯作者：
Morfini, Gerardo A.
中科院分区：
文献类型：
--
作者：
Kandan, Nicholas M.;Pigino, Gustavo F.;Brady, Scott T.;Lazarov, Orly;Binder, Lester I.;Morfini, Gerardo A.
关键词：
阿尔茨海默病（AD）的特征在于中枢神经系统中神经元的进行性、年龄依赖性变性。大量证据表明，AD中受影响的神经元遵循退行性变模式，其中突触功能和轴突连接的异常早于体细胞死亡。AD中神经元退行性变的潜在机制仍然难以捉摸，但已提出了几种机制，包括快速轴突运输（FAT）缺陷。因此，遗传证据将FAT的改变与神经元的退行性变联系起来，并且FAT缺陷已经在各种AD模型中被广泛记录。根据这些发现，我们讨论了实验证据，连接几个AD相关的致病性多肽异常激活的信号通路参与磷酸化调控的微管为基础的马达蛋白。虽然每种途径似乎以独特的方式影响FAT，但在AD的背景下，这些途径中的许多可能协同作用以损害对突触和轴突的维持和功能至关重要的分子组分的递送。旨在通过使特定蛋白激酶的活性正常化来预防FAT缺陷的治疗方法可能有助于预防AD中脆弱神经元的变性。
Alzheimer’s disease (AD) is characterized by progressive, age-dependent degeneration of neurons in the central nervous system. A large body of evidence indicates that neurons affected in AD follow a dying-back pattern of degeneration, where abnormalities in synaptic function and axonal connectivity long precede somatic cell death. Mechanisms underlying dying-back degeneration of neurons in AD remain elusive but several have been proposed, including deficits in fast axonal transport (FAT). Accordingly, genetic evidence linked alterations in FAT to dying-back degeneration of neurons, and FAT defects have been widely documented in various AD models. In light of these findings, we discuss experimental evidence linking several AD-related pathogenic polypeptides to aberrant activation of signaling pathways involved in the phosphoregulation of microtubule-based motor proteins. While each pathway appears to affect FAT in a unique manner, in the context of AD, many of these pathways might work synergistically to compromise the delivery of molecular components critical for the maintenance and function of synapses and axons. Therapeutic approaches aimed at preventing FAT deficits by normalizing the activity of specific protein kinases may help prevent degeneration of vulnerable neurons in AD.
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神经元中的自噬诱导和自噬体清除：与阿尔茨海默氏病自噬病理学的关系。
影响因子：
5.3
作者：
Boland, Barry;Kumar, Asok;Lee, Sooyeon;Platt, Frances M.;Wegiel, Jerzy;Yu, W. Haung;Nixon, Ralph A.
通讯作者：
Nixon, Ralph A.
影响因子：
1.7
作者：
Dessi, F;Colle, MA;Duyckaerts, C
通讯作者：
Duyckaerts, C
影响因子：
5.1
作者：
Brady, Scott;Morfini, Gerardo
通讯作者：
Morfini, Gerardo
影响因子：
25
作者：
Bosco, Daryl A.;Morfini, Gerardo;Karabacak, N. Murat;Song, Yuyu;Gros-Louis, Francois;Pasinelli, Piera;Goolsby, Holly;Fontaine, Benjamin A.;Lemay, Nathan;McKenna-Yasek, Diane;Frosch, Matthew P.;Agar, Jeffrey N.;Julien, Jean-Pierre;Brady, Scott T.;Brown, Robert H., Jr.
通讯作者：
Brown, Robert H., Jr.
影响因子：
16.2
作者：
Ashe, Karen H.;Zahs, Kathleen R.
通讯作者：
Zahs, Kathleen R.