Role of Rab GTPases in Alzheimer's Disease.,ACS Chemical Neuroscience

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Role of Rab GTPases in Alzheimer's Disease.
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2018-10-11 , DOI: 10.1021/acschemneuro.8b00387
Xian Zhang ₁ , Timothy Y Huang ₂ , Joel Yancey ₂ , Hong Luo ₁ , Yun-Wu Zhang ₁

Affiliation

Alzheimer's disease (AD) comprises two major pathological hallmarks: extraneuronal deposition of β-amyloid (Aβ) peptides ("senile plaques") and intraneuronal aggregation of the microtubule-associated protein tau ("neurofibrillary tangles"). Aβ is derived from sequential cleavage of the β-amyloid precursor protein by β- and γ-secretases, while aggregated tau is hyperphosphorylated in AD. Mounting evidence suggests that dysregulated trafficking of these AD-related proteins contributes to AD pathogenesis. Rab proteins are small GTPases that function as master regulators of vesicular transport and membrane trafficking. Multiple Rab GTPases have been implicated in AD-related protein trafficking, and their expression has been observed to be altered in postmortem AD brain. Here we review current implicated roles of Rab GTPase dysregulation in AD pathogenesis. Further elucidation of the pathophysiological role of Rab GTPases will likely reveal novel targets for AD therapeutics.

中文翻译：

Rab GTPases在阿尔茨海默氏病中的作用。

阿尔茨海默氏病（AD）包括两个主要病理特征：β淀粉样蛋白（Aβ）肽在神经外的沉积（“老年斑”）和微管相关蛋白tau（“神经原纤维缠结”）在神经内的聚集。Aβ源自β-和γ-分泌酶对β-淀粉样蛋白前体蛋白的连续切割，而聚集的tau在AD中被过度磷酸化。越来越多的证据表明这些AD相关蛋白的运输失调导致了AD的发病机理。Rab蛋白是小的GTP酶，起着水泡运输和膜运输的主要调节剂的作用。多个Rab GTPases已被证明与AD相关的蛋白质运输有关，并且在死后AD脑中已观察到它们的表达发生了改变。在这里，我们审查了Rab GTPase失调在AD发病机理中的当前牵连作用。Rab GTPases的病理生理作用的进一步阐明可能会揭示AD治疗的新目标。

更新日期：2018-09-27

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