title: Taking a risk: a therapeutic focus on ataxin-2 in amyotrophic lateral sclerosis?
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by the loss of lower and upper motor neurons leading to progressive muscle weakness and respiratory insufficiency. No treatment is currently available to cure ALS. Recent progress has led to the identification of several novel genetic determinants of this disease, including repeat expansions in the ataxin-2 (ATXN2) gene. Ataxin-2 is mislocalized in ALS patients and represents a relatively common susceptibility gene in ALS, making it a promising therapeutic target. In this review, we summarize genetic and pathological data implicating ataxin-2 in ALS, discuss potential disease mechanisms linked to altered ataxin-2 localization or function, and propose potential strategies for therapeutic intervention in ALS based on ataxin-2.
authors.affiliation: Department of Translational Neuroscience, UMC Utrecht Brain Center Rudolf Magnus, Utrecht, 3584 CG, The Netherlands; Department of Neurology and Neurosurgery, UMC Utrecht Brain Center Rudolf Magnus, Utrecht, 3584 CG, The Netherlands.
authors.forename: Dianne M A
authors.initials: DM
authors.lastname: van den Heuvel
authors.affiliation: Department of Translational Neuroscience, UMC Utrecht Brain Center Rudolf Magnus, Utrecht, 3584 CG, The Netherlands; Department of Neurology and Neurosurgery, UMC Utrecht Brain Center Rudolf Magnus, Utrecht, 3584 CG, The Netherlands.
authors.forename: Oliver
authors.initials: O
authors.lastname: Harschnitz
authors.affiliation: Department of Neurology and Neurosurgery, UMC Utrecht Brain Center Rudolf Magnus, Utrecht, 3584 CG, The Netherlands.
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
authors.affiliation: Department of Translational Neuroscience, UMC Utrecht Brain Center Rudolf Magnus, Utrecht, 3584 CG, The Netherlands. Electronic address: r.j.pasterkamp@umcutrecht.nl.
authors.forename: R Jeroen
authors.initials: RJ
authors.lastname: Pasterkamp
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D000818:Animals; D000067528:Ataxins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D009046:Motor Neurons / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D010455:Peptides; D011485:Protein Binding; D012313:RNA / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012307:Risk Factors; D019680:Trinucleotide Repeat Expansion
chemical_list: D000067528:Ataxins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D010455:Peptides; D018160:Receptors, Cytoplasmic and Nuclear; C097188:polyglutamine; D012313:RNA
keywords: FUS; TDP-43; amyotrophic lateral sclerosis; antisense oligonucleotide therapy; ataxin-2; neurodegeneration