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• W2945804912 abstract "Amyotrophic lateral sclerosis (ALS), also known as motor neurone disease, is an incurable neurodegenerative condition, characterized by the loss of upper and lower motor neurons. It affects 1-1.8/100,000 individuals worldwide, and the number of cases is projected to increase as the population ages. Thus, there is an urgent need to identify both therapeutic targets and disease-specific biomarkers - biomarkers that would be useful to diagnose and stratify patients into different sub-groups for therapeutic strategies, as well as biomarkers to follow the efficacy of any treatment tested during clinical trials. There is a lack of knowledge about pathogenesis and many hypotheses. Numerous ‘omics’ studies have been conducted on ALS in the past decade to identify a disease-signature in tissues and circulating biomarkers. The first goal of the present review was to group the molecular pathways that have been implicated in monogenic forms of ALS, to enable the description of patient strata corresponding to each pathway grouping. This strategy allowed us to suggest 14 strata, each potentially targetable by different pharmacological strategies. The second goal of this review was to identify diagnostic/prognostic biomarker candidates consistently observed across the literature. For this purpose, we explore previous biomarker-relevant ‘omics’ studies of ALS and summarize their findings, focusing on potential circulating biomarker candidates. We systematically review 118 papers on biomarkers published during the last decade. Several candidate markers were consistently shared across the results of different studies in either cerebrospinal fluid (CSF) or blood (leukocyte or serum/plasma). Although these candidates still need to be validated in a systematic manner, we suggest the use of combinations of biomarkers that would likely reflect the “health status” of different tissues, including motor neuron health (e.g. pNFH and NF-L, cystatin C, Transthyretin), inflammation status (e.g. MCP-1, miR451), muscle health (miR-338-3p, miR-206) and metabolism (homocysteine, glutamate, cholesterol). In light of these studies and because ALS is increasingly perceived as a multi-system disease, the identification of a panel of biomarkers that accurately reflect features of pathology is a priority, not only for diagnostic purposes but also for prognostic or predictive applications." @default.
• W2945804912 created "2019-05-29" @default.
• W2945804912 creator A5006246228 @default.
• W2945804912 creator A5026962542 @default.
• W2945804912 creator A5029301902 @default.
• W2945804912 creator A5033829611 @default.
• W2945804912 creator A5041703975 @default.
• W2945804912 creator A5078187049 @default.
• W2945804912 date "2019-05-14" @default.
• W2945804912 modified "2023-10-05" @default.
• W2945804912 title "A Systematic Review of Suggested Molecular Strata, Biomarkers and Their Tissue Sources in ALS" @default.
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