title: Emerging molecular biomarker targets for amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disease that affects upper (UMN) and lower motor (LMN) neurons. It is associated with a short survival and there is no effective treatment, in spite of a large number of clinical trials. Strong efforts have been made to identify novel disease biomarkers to support diagnosis, provide information on prognosis, to measure disease progression in trials and increase our knowledge on disease pathogenesis. Electromyography by testing the function of the LMN can be used as a biomarker of its dysfunction. A number of electrophysiological and neuroimaging methods have been explored to identify a reliable marker of UMN degeneration. Recently, strong evidence from independent groups, large cohorts of patients and multicenter studies indicate that neurofilaments are very promising diagnostic biomarkers, in particular cerebrospinal fluid and blood levels of phosphoneurofilament heavy chain and neurofilament light chain. Furthermore, their increased levels are associated with poor prognosis. Additional studies have been performed aiming to identify other biomarkers, which alone or in combination with neurofilaments could increase the sensitivity and the specificity of the assays. Emerging molecular marker targets are being discovered, but more studies with standardized methods are required in larger cohorts of ALS patients.
authors.affiliation: Laboratory of Glycobiology, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Avenida da República, 2780-157 Oeiras, Portugal. Electronic address: jcosta@itqb.unl.pt.
authors.forename: Júlia
authors.initials: J
authors.lastname: Costa
authors.affiliation: Institute of Physiology-Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Portugal; Department Neurosciences, Hospital de Santa Maria-CHLN, Lisbon, Portugal.
authors.forename: Mamede
authors.initials: M
authors.lastname: de Carvalho
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D002648:Child; D006801:Humans
chemical_list: D015415:Biomarkers
keywords: Amyotrophic lateral sclerosis; Biomarker; Neurofilaments; Progression; Survival