The dysregulation of intracellular calcium in Alzheimer disease.
The dysregulation of intracellular calcium in Alzheimer disease.
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DOI：
10.1016/j.ceca.2009.12.014
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发表时间：
2010-02
期刊：
影响因子：
4
通讯作者：
Bezprozvanny I
中科院分区：
文献类型：
--
作者：
Supnet C;Bezprozvanny I
阿尔茨海默病（Alzheimer disease，AD）是世界范围内最常见的神经退行性疾病，目前尚无法治愈。毒性淀粉样蛋白-β（Aβ）肽聚集体在AD脑中的积累被认为触发与认知下降相关的广泛突触丧失和神经变性，这一想法是家族性（FAD）和散发性形式的AD病因学的“淀粉样蛋白假说”的基础。引起FAD的突变还导致神经元钙（Ca 2+）处理的失调，并可能有助于AD发病机制，这一想法称为AD的“钙假说”。特别是，AD小鼠模型中内质网（ER）引起的Ca 2+失调导致胞质Ca 2+水平升高，这可能触发对神经元功能和健康有害的信号级联反应。然而，越来越多的证据表明，并不是所有形式的AD神经元中的Ca 2+失调都是有害的，其中一些可能是代偿性的。这些变化可能有助于调节神经元兴奋性和减缓AD病理，特别是在疾病的早期阶段。显然，需要更好地理解神经元Ca 2+处理的失调如何有助于AD中的神经变性和神经保护，因为Ca 2+信号传导调节剂是作为潜在AD治疗剂的非常感兴趣的靶点。
Alzheimer disease (AD) is the most common neurodegenerative disorder worldwide and is at present, incurable. The accumulation of toxic amyloid-beta (Aβ) peptide aggregates in AD brain are thought to trigger the extensive synaptic loss and neurodegeneration linked to cognitive decline, an idea that underlies the ‘amyloid hypothesis’ of AD etiology in both the familal (FAD) and sporadic forms of the disease. Mutations causing FAD also result in the dysregulation of neuronal calcium (Ca2+) handling and may contribute to AD pathogenesis, an idea termed the ‘calcium hypothesis’ of AD. In particular, Ca2+ dysregulation by the endoplasmic reticulum (ER) in AD mouse models results in augmented cytosolic Ca2+ levels which can trigger signaling cascades that are detrimental to neuronal function and health. However, there is growing evidence to suggest that not all forms of Ca2+ dysregulation in AD neurons are harmful and some of them instead may be compensatory. These changes may help modulate neuronal excitability and slow AD pathology, especially in the early stages of the disease. Clearly, a better understanding of how dysregulation of neuronal Ca2+ handling contributes to neurodegeneration and neuroprotection in AD is needed as Ca2+ signaling modulators are targets of great interest as potential AD therapeutics.
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影响因子：
4.7
作者：
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通讯作者：
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影响因子：
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