Amyloid precursor protein and alpha synuclein translation, implications for iron and inflammation in neurodegenerative diseases.
Amyloid precursor protein and alpha synuclein translation, implications for iron and inflammation in neurodegenerative diseases.
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DOI：
10.1016/j.bbagen.2008.12.001
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发表时间：
2009-07
影响因子：
3
通讯作者：
Rogers, Jack T.
中科院分区：
文献类型：
--
作者：
Cahill, Catherine M.;Lahiri, Debomoy K.;Huang, Xudong;Rogers, Jack T.
最近的研究表明，血色病基因中的等位基因可能会加速阿尔茨海默病（AD）的发病5年，这证实了人们对金属（特别是铁）加速疾病进程的模型的兴趣。生物化学和生物物理测量表明，AD患者的大脑中存在神经毒性铜，锌和铁的水平升高。淀粉样前体蛋白（APP）全蛋白的细胞内水平被证明是通过铁调节，其机制类似于铁响应元件（IRE）RNA茎环在其5′非翻译区（5′ UTR）中对铁蛋白L-和H mRNA的翻译控制。最近，我们报道了一个假定的IRE样序列存在于帕金森病（PD）特异性α突触核蛋白（ASYN）转录本的5′UTR。ASYN编码淀粉样斑块的非A β组分（NAC）。APP mRNA的铁依赖性翻译、AD患者斑块中金属的参与以及PD患者黑质（SN）中纹状体神经元中铁的增加的证明，均鼓励开发金属衰减剂和铁螯合剂作为治疗这些神经退行性疾病的主要新治疗策略。在AD的情况下，基于金属的治疗剂可能最终被证明比使用淀粉样蛋白疫苗作为改善AD患者的认知下降的优选抗淀粉样蛋白治疗策略更具成本效益。
Recent studies that alleles in the hemochromatosis gene may accelerate the onset of Alzheimer's disease (AD) by five years have validated interest in the model in which metals (particularly iron) accelerate disease course. Biochemical and biophysical measurements demonstrated the presence of elevated levels of neurotoxic copper, zinc and iron in the brains of AD patients. Intracellular levels of amyloid precursor protein (APP) holoprotein were shown to be modulated via iron by a mechanism that is similar to the translation control of the ferritin L- and H mRNAs by Iron-responsive Element (IRE) RNA stem loops in their 5′untranslated regions (5′UTRs). Recently, we reported a putative IRE-like sequence to be present in the 5′UTR of the Parkinson's disease (PD) specific alpha synuclein (ASYN) transcript. ASYN encodes the non-Aβ component (NAC) of amyloid plaques. The demonstration of iron-dependent translation of APP mRNA, the involvement of metals in the plaque of AD patients and of increased iron in striatal neurons in the Substantia nigra (SN) of PD patients, have each encouraged the development of metal attenuating agents and iron chelators as a major new therapeutic strategy for the treatment of these neurodegenerative diseases. In the case of AD, metal based therapeutics may ultimately prove more cost effective than the use of an amyloid vaccine as the preferred anti-amyloid therapeutic strategy to ameliorate the cognitive decline of AD patients.
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影响因子：
4.8
作者：
Buxbaum, JD;Liu, KN;Black, RA
通讯作者：
Black, RA
影响因子：
--
作者：
Bandyopadhyay, Sanghamitra;Ni, Jake;Rogers, Jack T.
通讯作者：
Rogers, Jack T.
影响因子：
56.9
作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
4.2
作者：
Bandyopadhyay, Sanghamitra;Hartley, Dean M.;Rogers, Jack T.
通讯作者：
Rogers, Jack T.