Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by the progressive loss of lower motor neurons, weakness and muscle atrophy. ALS lacks an effective cure and diagnosis is often made by exclusion. Thus, it is imperative to search for biomarkers. Biomarkers can help in understanding ALS pathomechanisms, identification of targets for treatment and development of effective therapies. Peripheral blood mononuclear cells (PBMCs) represent a valid source for biomarkers compared to cerebrospinal fluid, as they are simple to collect, and to plasma, because of the possibility of detecting lower expressed proteins. They are a reliable model for patients’ stratification. This review provides an overview on PBMCs as a potential source of biomarkers in ALS. We focused on altered RNA metabolism (coding/non-coding RNA), including RNA processing, mRNA stabilization, transport and translation regulation. We addressed protein abnormalities (aggregation, misfolding and modifications); specifically, we highlighted that SOD1 appears to be the most characterizing protein in ALS. Finally, we emphasized the correlation between biological parameters and disease phenotypes, as regards prognosis, severity and clinical features. In conclusion, even though further studies are needed to standardize the use of PBMCs as a tool for biomarker investigation, they represent a promising approach in ALS research.
Highlights
Biomarkers can help in understanding Amyotrophic lateral sclerosis (ALS) pathomechanisms, identification of targets for treatment and development of effective therapies
This review provides an overview on Peripheral blood mononuclear cells (PBMCs) as a potential source of biomarkers in ALS
Even though further studies are needed to standardize the use of PBMCs as a tool for biomarker investigation, they represent a promising approach in ALS research
Summary
Neurodegenerative diseases (NDDs) are a broad group of debilitating pathologies that affect specific types of neural cells, leading to their death. Because of the increasing average age of the population, these age-related disorders are becoming more prevalent They are different in their manifestations, due to the distinct types of affected cells and the variability of the pathophysiology. They share common features: they can manifest in two main forms, sporadic and familiar, that may or may not be characterized by specific gene mutations, and they all lead to the accumulation of disease-specific proteins [1,2]. Mutations in the VCP gene, involved in both ALS and FTD, manifest ubiquitin and TDP-43 inclusions, and are grouped in the so-called proteinopathies [27]. Thanks to the advancements in GWAS technology, many ALS-associated SNPs are known [33,34] and, more recently, Zhang and colleagues found a correlation between CpG-SNPs and ALS age of onset [35]
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