Zn II(atsm) is protective in amyotrophic lateral sclerosis model mice via a copper delivery mechanism

Neurobiology of Disease
Erin J McAllumPeter J Crouch

Abstract

Mutations in the metalloprotein Cu,Zn-superoxide dismutase (SOD1) cause approximately 20% of familial cases of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease for which effective therapeutics do not yet exist. Transgenic rodent models based on over-expression of mutant SOD1 have been developed and these have provided opportunity to test new therapeutic strategies and to study the mechanisms of mutant SOD1 toxicity. Although the mechanisms of mutant SOD1 toxicity are yet to be fully elucidated, incorrect or incomplete metallation of SOD1 confers abnormal folding, aggregation and biochemical properties, and improving the metallation state of SOD1 provides a viable therapeutic option. The therapeutic effects of delivering copper (Cu) to mutant SOD1 have been demonstrated recently. The aim of the current study was to determine if delivery of zinc (Zn) to SOD1 was also therapeutic. To investigate this, SOD1G37R mice were treated with the metal complex diacetyl-bis(4-methylthiosemicarbazonato)zinc(II) [Zn(II)(atsm)]. Treatment resulted in an improvement in locomotor function and survival of the mice. However, biochemical analysis of spinal cord tissue collected from the mice revealed that the treatment did not ...Continue Reading

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Citations

Mar 26, 2016·European Journal of Medicinal Chemistry·Elisse C Browne, Belinda M Abbott
Aug 9, 2016·Journal of Molecular Neuroscience : MN·Erin J McAllum, David I Finkelstein
Nov 7, 2015·Neurobiology of Disease·Elias Aizenman, Pier G Mastroberardino
Jun 10, 2017·Expert Reviews in Molecular Medicine·Francisco J Gil-BeaAinara Vallejo-Illarramendi
Jan 16, 2018·Chemistry : a European Journal·Amandine Conte-DabanChristelle Hureau
Aug 23, 2018·Frontiers in Neuroscience·Rossana SirabellaGiuseppe Pignataro
Oct 28, 2019·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Karla AcevedoAshley I Bush

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