Department of (Neuro)Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, 1105 AZ Amsterdam, The Netherlands.
Neurodegenerative Disorders Collaborative Laboratory, RIKEN Center for Brain Science, Saitama 351-0106, Japan.
Genes (Basel). 2022 Jun 9;13(6):1034. doi: 10.3390/genes13061034.
To date, no neurodegenerative diseases (NDDs) have cures, and the underlying mechanism of their pathogenesis is undetermined. As miRNAs extensively regulate all biological processes and are crucial regulators of healthy brain function, miRNAs differentially expressed in NDDs may provide insight into the factors that contribute to the emergence of protein inclusions and the propagation of deleterious cellular environments. A meta-analysis of miRNAs dysregulated in Alzheimer's disease, Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies and frontotemporal lobar degeneration (TDP43 variant) was performed to determine if diseases within a proteinopathy have distinct or shared mechanisms of action leading to neuronal death, and if proteinopathies can be classified on the basis of their miRNA profiles. Our results identified both miRNAs distinct to the anatomy, disease type and pathology, and miRNAs consistently dysregulated within single proteinopathies and across neurodegeneration in general. Our results also highlight the necessity to minimize the variability between studies. These findings showcase the need for more transcriptomic research on infrequently occurring NDDs, and the need for the standardization of research techniques and platforms utilized across labs and diseases.
迄今为止,尚无针对神经退行性疾病 (NDD) 的治愈方法,其发病机制也尚未确定。miRNA 广泛调节所有生物过程,是健康大脑功能的重要调节剂,因此在 NDD 中表达异常的 miRNA 可能有助于深入了解导致蛋白包涵体形成和有害细胞环境传播的因素。对阿尔茨海默病、帕金森病、多系统萎缩、进行性核上性麻痹、皮质基底节变性、路易体痴呆和额颞叶变性(TDP43 变异)中失调的 miRNA 进行荟萃分析,以确定蛋白质病中是否存在导致神经元死亡的不同或共同作用机制,如果可以根据其 miRNA 谱对蛋白质病进行分类。我们的研究结果确定了特定于解剖结构、疾病类型和病理学的 miRNA,以及在单一蛋白质病和整个神经退行性变中普遍失调的 miRNA。我们的研究结果还强调了有必要减少研究之间的变异性。这些发现突显了对罕见 NDD 进行更多转录组研究的必要性,以及跨实验室和疾病标准化研究技术和平台使用的必要性。