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INTRODUCTION: Proteomic analysis has contributed significantly to the study of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). It has helped to define the pathological change common to nearly all cases, namely intracellular aggregates of phosphorylated TDP-43, shifting the focus of pathogenesis in ALS toward RNA biology. Proteomics has also uniquely underpinned the delineation of disease mechanisms in model systems and has been central to recent advances in human ALS biomarker development. AREAS COVERED: The contribution of proteomics to understanding the cellular pathological changes, disease mechanisms, and biomarker development in ALS are covered. EXPERT OPINION: Proteomics has delivered unique insights into the pathogenesis of ALS and advanced the goal of objective measurements of disease activity to improve therapeutic trials. Further developments in sensitivity and quantification are expected, with application to the presymptomatic phase of human disease offering the hope of prevention strategies.

Original publication

DOI

10.1080/14789450.2021.2004890

Type

Journal article

Journal

Expert Rev Proteomics

Publication Date

11/2021

Volume

18

Pages

977 - 994

Keywords

Amyotrophic lateral sclerosis, C9orf72, SOD1, TDP-43, biomarkers, cerebrospinal fluid, neurodegeneration, proteomics, Amyotrophic Lateral Sclerosis, Biomarkers, Humans, Neurodegenerative Diseases, Proteomics