The non-protein amino acid BMAA is misincorporated into human proteins in place of L-serine causing protein misfolding and aggregation.
The non-protein amino acid BMAA is misincorporated into human proteins in place of L-serine causing protein misfolding and aggregation.
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DOI：
10.1371/journal.pone.0075376
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Rodgers KJ
中科院分区：
文献类型：
--
作者：
Dunlop RA;Cox PA;Banack SA;Rodgers KJ
蛋白质错误折叠的机制在以蛋白质聚集和缠结为特征的神经退行性疾病的病因学中引起越来越多的兴趣，所述神经退行性疾病包括肌萎缩性侧索硬化症（ALS）、阿尔茨海默病（AD）、帕金森病（PD）、路易体痴呆（LBD）和进行性核上性麻痹（PSP）。某些形式的神经退行性疾病与控制疾病相关蛋白质组装的基因突变有关。例如，小鼠粘性突变sti，其导致未检测到的tRNAAla与丝氨酸的误充电，导致蛋白质中丝氨酸取代丙氨酸，导致实验室动物的小脑浦肯野细胞损失和共济失调。在tau中用谷氨酸替换丝氨酸422增加了与神经变性相关的tau聚集的倾向。然而，环境因素可能引发蛋白质异常折叠的可能性仍然相对未被探索。我们在这里报告，非蛋白质氨基酸，β-N-甲氨基-L-丙氨酸（BMAA），可以错误地取代L-丝氨酸进入人类蛋白质。我们还报告说，这种错误的掺入可以抑制L-丝氨酸。将BMAA错误掺入人类神经蛋白中可能会揭示人类暴露于蓝藻产生的BMAA与ALS发病率增加之间的假定关联。
Mechanisms of protein misfolding are of increasing interest in the aetiology of neurodegenerative diseases characterized by protein aggregation and tangles including Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s disease (AD), Parkinson’s disease (PD), Lewy Body Dementia (LBD), and Progressive Supranuclear Palsy (PSP). Some forms of neurodegenerative illness are associated with mutations in genes which control assembly of disease related proteins. For example, the mouse sticky mutation sti, which results in undetected mischarging of tRNAAla with serine resulting in the substitution of serine for alanine in proteins causes cerebellar Purkinje cell loss and ataxia in laboratory animals. Replacement of serine 422 with glutamic acid in tau increases the propensity of tau aggregation associated with neurodegeneration. However, the possibility that environmental factors can trigger abnormal folding in proteins remains relatively unexplored. We here report that a non-protein amino acid, β-N-methylamino-L-alanine (BMAA), can be misincorporated in place of l-serine into human proteins. We also report that this misincorporation can be inhibited by l-serine. Misincorporation of BMAA into human neuroproteins may shed light on putative associations between human exposure to BMAA produced by cyanobacteria and an increased incidence of ALS.
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影响因子：
5.4
作者：
Mondo K;Hammerschlag N;Basile M;Pablo J;Banack SA;Mash DC
通讯作者：
Mash DC
影响因子：
4.7
作者：
Haase, C;Stieler, JT;Holzer, M
通讯作者：
Holzer, M
DOI：
10.1073/pnas.2235808100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Cox, PA;Banack, SA;Murch, SJ
通讯作者：
Murch, SJ
影响因子：
--
作者：
Bell, E. Arthur
通讯作者：
Bell, E. Arthur
影响因子：
2.8
作者：
Banack, S. A.;Metcalf, J. S.;Cox, P. A.
通讯作者：
Cox, P. A.