Molecular & Cell Biology, University of Cape Town, Private Bag, Rondebosch, Cape Town 7700, South Africa.
Int J Mol Sci. 2021 Oct 5;22(19):10757. doi: 10.3390/ijms221910757.
Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with extensive genetic and aetiological heterogeneity. While the underlying molecular mechanisms involved remain unclear, significant progress has been facilitated by recent advances in high-throughput transcriptomic, epigenomic and proteomic technologies. Here, we review recently published ASD proteomic data and compare proteomic functional enrichment signatures with those of transcriptomic and epigenomic data. We identify canonical pathways that are consistently implicated in ASD molecular data and find an enrichment of pathways involved in mitochondrial metabolism and neurogenesis. We identify a subset of differentially expressed proteins that are supported by ASD transcriptomic and DNA methylation data. Furthermore, these differentially expressed proteins are enriched for disease phenotype pathways associated with ASD aetiology. These proteins converge on protein-protein interaction networks that regulate cell proliferation and differentiation, metabolism, and inflammation, which demonstrates a link between canonical pathways, biological processes and the ASD phenotype. This review highlights how proteomics can uncover potential molecular mechanisms to explain a link between mitochondrial dysfunction and neurodevelopmental pathology.
自闭症谱系障碍（ASD）是一种复杂的神经发育障碍，具有广泛的遗传和病因异质性。尽管涉及的潜在分子机制尚不清楚，但高通量转录组学、表观基因组学和蛋白质组学技术的最新进展为我们提供了便利。在这里，我们回顾了最近发表的 ASD 蛋白质组学数据，并将蛋白质组学功能富集特征与转录组学和表观基因组学数据进行了比较。我们确定了在 ASD 分子数据中始终存在的经典途径，并发现了与线粒体代谢和神经发生相关的途径的富集。我们鉴定了一组差异表达蛋白，这些蛋白得到了 ASD 转录组学和 DNA 甲基化数据的支持。此外，这些差异表达蛋白富集了与 ASD 病因相关的疾病表型途径。这些蛋白质集中在调节细胞增殖和分化、代谢和炎症的蛋白质-蛋白质相互作用网络上，这表明了经典途径、生物学过程和 ASD 表型之间的联系。本综述强调了蛋白质组学如何揭示潜在的分子机制，以解释线粒体功能障碍与神经发育病理学之间的联系。
