TMEM106B Fibrils from FTLD Patients and Healthy Controls.
TMEM106B Fibrils from FTLD Patients and Healthy Controls.
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DOI：
10.1021/acschemneuro.3c00482
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发表时间：
2023-08-16
影响因子：
5
通讯作者：
Walczak, Maciej A.
中科院分区：
文献类型：
--
作者：
Greenwood, James D.;Powell, Wyatt C.;Walczak, Maciej A.
涉及四个研究团队的近期研究表明，额颞叶变性伴TDP - 43蛋白包涵体（FTLD - TDP）患者以及认知健康个体中的淀粉样纤维主要由跨膜蛋白106B（TMEM106B）组成，该蛋白先前被确定为FTLD - TDP的一个风险因素。通过低温电子显微镜，这些研究确定了来自几种神经退行性疾病患者的TMEM106B纤维的各种原丝结构。这些发现为未来的研究提出了新的问题和机遇，因为它们表明TMEM106B在FTLD病理中起着核心作用。这些发现还促使有必要开发针对纤维状TMEM106B的特异性抗体，并需要进一步研究TMEM106B与其他丝状聚集体之间潜在的机制联系。低温电子显微镜技术的强大作用在这些意外发现中得以凸显，并且它可能是进一步深入了解以淀粉样沉积物为特征的神经退行性疾病分子机制的重要工具。
Recent studies involving four research teams have revealed that amyloid fibrils in FTLD-TDP patients and cognitively healthy individuals primarily consist of TMEM106B, a protein previously identified as a risk factor for FTLD-TDP. Through cryogenic electron microscopy, the studies identified various protofilament structures of TMEM106B fibrils from individuals with several neurodegenerative diseases. These findings raise new questions and opportunities for future research, as they suggest that TMEM106B plays a central role in FTLD pathology. These discoveries also prompt the need for the development of specific antibodies for fibrillar TMEM106B and necessitate further investigation of the potential mechanistic link between TMEM106B and other filamentous aggregates. The power of cryo-EM techniques is underscored in these unexpected findings and may be a vital tool for gaining further molecular insights into neurodegenerative diseases characterized by amyloid deposits.
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