Pasternack Nicholas, Doucet-O'Hare Tara, Johnson Kory, Paulsen Ole, Nath Avindra
Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD, USA.
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
iScience. 2024 May 28;27(7):110147. doi: 10.1016/j.isci.2024.110147. eCollection 2024 Jul 19.
Amyotrophic lateral sclerosis (ALS) is a universally fatal neurodegenerative disease with no cure. Human endogenous retroviruses (HERVs) have been implicated in its pathogenesis but their relevance to ALS is not fully understood. We examined bulk RNA-seq data from almost 2,000 ALS and unaffected control samples derived from the cortex and spinal cord. Using different methods of feature selection, including differential expression analysis and machine learning, we discovered that transcription of HERV-K loci 1q22 and 8p23.1 were significantly upregulated in the spinal cord of individuals with ALS. Additionally, we identified a subset of ALS patients with upregulated HERV-K expression in the cortex and spinal cord. We also found the expression of HERV-K loci 19q11 and 8p23.1 was correlated with protein coding genes previously implicated in ALS and dysregulated in ALS patients in this study. These results clarify the association of HERV-K and ALS and highlight specific genes in the pathobiology of late-stage ALS.
肌萎缩侧索硬化症（ALS）是一种无法治愈的、普遍致命的神经退行性疾病。人类内源性逆转录病毒（HERV）被认为与该疾病的发病机制有关，但其与ALS的相关性尚未完全明确。我们研究了来自近2000份ALS患者以及未受影响的对照样本的大量RNA测序数据，这些样本取自大脑皮层和脊髓。通过使用不同的特征选择方法，包括差异表达分析和机器学习，我们发现HERV-K基因座1q22和8p23.1在ALS患者脊髓中的转录显著上调。此外，我们鉴定出了一部分在大脑皮层和脊髓中HERV-K表达上调的ALS患者。我们还发现，HERV-K基因座19q11和8p23.1的表达与先前在ALS中涉及的蛋白质编码基因相关，并且在本研究中ALS患者中表达失调。这些结果阐明了HERV-K与ALS的关联，并突出了晚期ALS病理生物学中的特定基因。
