Gene expression profiling in peripheral blood mononuclear cells from patients with sporadic amyotrophic lateral sclerosis (sALS)

Abstract

The aim of this study was to identify gene expression profiles in peripheral blood mononuclear cells (PBMCs) from sporadic amyotrophic lateral sclerosis (sALS) patients to gain insights into the pathogenesis of ALS. We found that upregulation of LPS/TLR4-signaling associated genes was observed in the PMBCs from sALS patients after short-term cultivation, and that elevated levels of gene expression correlated with degree of peripheral blood monocyte activation and plasma LPS levels in sALS. Similar patterns of gene expression were reproduced in LPS stimulated PBMCs from healthy controls. These data suggest that chronic monocyte/macrophage activation may be through LPS/TLR4-signaling pathways in ALS.

Mitochondrial Oxidative Phosphorylation Transcriptome Alterations in Human Amyotrophic Lateral Sclerosis Spinal Cord and Blood

“…In ALS research, while there have been several transcriptomic studies of central nervous and peripheral human tissues, animal and cell models, the complete picture is still being elucidated. Large lists of differentially expressed genes have been generated (Dangond et al 2004;Jiang et al 2005;Malaspina and de Belleroche 2004;Malaspina et al 2001;Rabin et al 2010;Saris et al 2009;Wang et al 2006;Zhang et al 2011), and although there are discrepancies between individual members of gene lists, there is a high degree of overlap in the molecular pathways predicted to be involved in this complex disease (Henriques and Gonzalez De Aguilar 2011;Heath et al 2013).…”

Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory Hypothesis in Amyotrophic Lateral Sclerosis Revisited

“…For example, circulating myeloid cells of ALS patients have a proinflammatory phenotype [90,176], while regulatory T lymphocytes are decreased, enhancing neuroinflammation and disease progression [177]. Also, the up-regulation of inflammatory genes in arrays on samples from ALS patients suggests the involvement of immune actions in the ALS pathogenesis [178][179][180]. Some other studies have related motor neuron disease with autoimmune neuromuscular disorders.…”

Insights Arising from Gene Expression Profiling in Amyotrophic Lateral Sclerosis

“…Gene expression profiling has been conducted on blood and fibroblasts from ALS patients (Highley et al 2011;Saris et al 2009;Zhang et al 2011). Microarray analysis of SALS and control blood samples was followed by hierarchical clustering of all genes found to be significantly expressed in all samples after normalisation (Saris et al 2009).…”

“…In addition, there was a correlation with the CNS tissue studies, as the blood in ALS patients showed a decrease in genes associated with protein processing and RNA post-transcriptional modification, as well as increases in genes associated with inflammation. A more recent study performed gene expression profiling on peripheral blood mononuclear cells from patients with SALS (Zhang et al 2011). These cells showed an up-regulation of genes associated with immune activation in response to lipopolysaccharide (LPS), which correlated with an elevation of plasma LPS.…”