Advancing mechanistic understanding and biomarker development in amyotrophic lateral sclerosis

Authors

Alexander G. Thompson, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Patrick Oeckl, Department of Neurology, University of Ulm, Ulm, Germany.
Emily Feneberg, Department of Neurology, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany.
Robert Bowser, Departments of Neurology and Translational Neuroscience, Barrow Neurological Institute, Phoenix, Arizona, USA.Follow
Markus Otto, Department of Neurology, University of Ulm, Ulm, Germany.
Roman Fischer, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Benedikt Kessler, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Martin R. Turner, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.

Document Type

Article

Abstract

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.

Keywords

Amyotrophic lateral sclerosis, C9orf72, SOD1, TDP-43, biomarkers, cerebrospinal fluid, neurodegeneration, proteomics

Medical Subject Headings

Amyotrophic Lateral Sclerosis (genetics); Biomarkers; Humans; Neurodegenerative Diseases; Proteomics

Publication Date

11-1-2021

Publication Title

Expert review of proteomics

E-ISSN

1744-8387

Volume

18

Issue

11

First Page

977

Last Page

994

PubMed ID

34758687

Digital Object Identifier (DOI)

10.1080/14789450.2021.2004890

Recommended Citation

Thompson, Alexander G.; Oeckl, Patrick; Feneberg, Emily; Bowser, Robert; Otto, Markus; Fischer, Roman; Kessler, Benedikt; and Turner, Martin R., "Advancing mechanistic understanding and biomarker development in amyotrophic lateral sclerosis" (2021). Translational Neuroscience. 2306.
https://scholar.barrowneuro.org/neurobiology/2306