蛋白质受损和性别差异

支持Brain Awareness Week,,,,we’re highlighting some of the amazing benefits of brain research and showcasing the progress being made by researchers around the world (learn morehere)。分子大脑todaypublishes research探索性别差异的分子基础s in dementia, focusing on Alzheimer’s with cerebrovascular disease. Co-author Xavier Gallart-Palau explains more in this guest blog.

The silent epidemic

我仍然记得我祖母不再能够识别我的脸的那一刻。当我年轻的时候,她教我如何骑自行车,她读了我的书,当我摔倒时照顾我。这些记忆的感情也被遗忘了吗?不幸的是,我们永远不会知道,因为她很快无法解释她的脑海。这种毁灭性的经历鼓励我研究颞痴呆的基础。

Dementia is considered the ‘silent epidemic’ of the 21英石century which is currently affecting almost 50 million全球人。Around the world, a new case of dementia is diagnosed every 3.2 seconds on average, where Alzheimer’s disease is themajor contributor对这种全球流行病。

根据美国阿尔茨海默氏症协会和澳大利亚卫生与福利研究所的最新报道,,,,two thirds ofpatients diagnosed with Alzheimer’s是女人。在80岁年龄段的人群中,该比率增加到75%。

研究痴呆的分子基础

The molecular basis of gender differences on the prevalence of dementia remained understudied for a long time.

The molecular basis of gender differences on the prevalence of dementia remained understudied for a long time. If we want to beat our adversary we need to know it in depth, therefore, the development of effective new therapies for patients with dementia will require a better understanding of the neurodegenerative pathology at the molecular level.

Although we are still at a very early stage of neurodegenerative research there is room for hope as not all that we find is bad news.动物模型研究表明,如果我们对神经退行性的分子基础有更好的了解,则衰老对脑神经元和认知功能的影响可能是可逆的。

使用蛋白质组学来识别阿尔茨海默氏症的性别差异

A good field to decipher the molecular basis of neurodegeneration from an unbiased discovery-driven approach isproteomics,蛋白质的大规模研究。这个高通量技术领域允许表征验尸后脑样本的数千种蛋白质的水平和成分。

A new study directed by Professor Sze Siu Kwan and published in分子大脑采用了发现驱动的蛋白质组学,以解读阿尔茨海默氏症性别差异的分子基础,患有脑血管疾病(CVD),这是老年人中最常见的痴呆症相关神经退行性疾病。

在全球评估男性,痴呆症和年龄匹配对照的男性尸体后脑组织中的1500多种蛋白质之后,我们发现了与性别相关的髓磷脂和线粒体蛋白的调节。

在这项研究中,在全球评估男性,痴呆症和年龄匹配对照的男性尸体后脑组织的1500多种蛋白质之后,我们发现了与性别相关的髓磷脂和线粒体蛋白的调节。

Altered proteins

痴呆症女性发现白质的损害更高,尽管几种髓磷脂蛋白的水平也更高。这一事实表明该组中的透明度反应不正确。恢复性受损可能与较高的发生degenerative protein modificationsin the key white matter protein, also known as myelin basic protein (MBP).

退化性蛋白质修饰改变了蛋白质的电荷和分子组成。结果,这会损害其结构和功能。发现MBP受到退化性蛋白质修饰的高度影响脱真正and柠檬化在阿尔茨海默氏症的颞叶中,有CVD女性患者。

与痴呆症男性相比,痴呆症女性的MBP较高的MBP促进了功能失调的MBP的积累,从而导致再生反应受损。这个事实可能直接对痴呆症的认知表现产生影响。

线粒体是负责向脑细胞供应能量的细胞器,在痴呆症女性中也比男性更受损。这表明该组神经元对细胞死亡的脆弱性更高。

The future of dementia treatment

退化性蛋白质修饰是“可药物”靶标,如果我们进一步了解它们对健康和功能障碍蛋白的影响,则有望治疗痴呆症。

退化性蛋白质修饰是“可药物”靶标,如果我们进一步了解它们对健康和功能障碍蛋白的影响,则有望治疗痴呆症。As it was found in this study, degenerative protein modifications seem to play a crucial role in the molecular basis of gender differences in Alzheimer’s with CVD.

Similarly, the temporal and functional relationships established between white matter disease and mitochondria dysfunction in Alzheimer’s with CVD seem to act as a crucial event of the neurodegenerative process and requires further attention in future research.


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