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Integrated elemental analysis supports targeting copper perturbations as a therapeutic strategy in multiple sclerosis.
Hilton, James B W; Kysenius, Kai; Liddell, Jeffrey R; Mercer, Stephen W; Rautengarten, Carsten; Hare, Dominic J; Buncic, Gojko; Paul, Bence; Murray, Simon S; McLean, Catriona A; Kilpatrick, Trevor J; Beckman, Joseph S; Ayton, Scott; Bush, Ashley I; White, Anthony R; Roberts, Blaine R; Donnelly, Paul S; Crouch, Peter J.
Afiliación
  • Hilton JBW; Department of Anatomy & Physiology, The University of Melbourne, Victoria 3010, Australia.
  • Kysenius K; Department of Anatomy & Physiology, The University of Melbourne, Victoria 3010, Australia; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria 3010, Australia.
  • Liddell JR; Department of Anatomy & Physiology, The University of Melbourne, Victoria 3010, Australia.
  • Mercer SW; Department of Anatomy & Physiology, The University of Melbourne, Victoria 3010, Australia.
  • Rautengarten C; School of Biosciences, The University of Melbourne, Victoria 3010, Australia.
  • Hare DJ; Atomic Medicine Initiative, University of Technology Sydney, Australia.
  • Buncic G; School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia.
  • Paul B; School of Geography, Earth and Atmospheric Sciences, The University of Melbourne, Victoria 3010, Australia; Elemental Scientific Lasers, LLC, 685 Old Buffalo Trail, Bozeman, MT 59715, United States.
  • Murray SS; Department of Anatomy & Physiology, The University of Melbourne, Victoria 3010, Australia.
  • McLean CA; Anatomical Pathology, The Alfred Hospital, Victoria 3004, Australia.
  • Kilpatrick TJ; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria 3010, Australia.
  • Beckman JS; Linus Pauling Institute, Department of Biochemistry and Biophysics, Oregon State University, 97331, United States.
  • Ayton S; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria 3010, Australia; Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria 3010, Australia.
  • Bush AI; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria 3010, Australia; Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria 3010, Australia.
  • White AR; Queensland Institute of Medical Research Berghofer, Herston, Queensland 4006, Australia.
  • Roberts BR; Department of Biochemistry, Emory University, Atlanta, GA 30322, United States.
  • Donnelly PS; School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia.
  • Crouch PJ; Department of Anatomy & Physiology, The University of Melbourne, Victoria 3010, Australia. Electronic address: pjcrouch@unimelb.edu.au.
Neurotherapeutics ; : e00432, 2024 Aug 19.
Article en En | MEDLINE | ID: mdl-39164165
ABSTRACT
Multiple sclerosis (MS) is a debilitating affliction of the central nervous system (CNS) that involves demyelination of neuronal axons and neurodegeneration resulting in disability that becomes more pronounced in progressive forms of the disease. The involvement of neurodegeneration in MS underscores the need for effective neuroprotective approaches necessitating identification of new therapeutic targets. Herein, we applied an integrated elemental analysis workflow to human MS-affected spinal cord tissue utilising multiple inductively coupled plasma-mass spectrometry methodologies. These analyses revealed shifts in atomic copper as a notable aspect of disease. Complementary gene expression and biochemical analyses demonstrated that changes in copper levels coincided with altered expression of copper handling genes and downstream functionality of cuproenzymes. Copper-related problems observed in the human MS spinal cord were largely reproduced in the experimental autoimmune encephalomyelitis (EAE) mouse model during the acute phase of disease characterised by axonal demyelination, lesion formation, and motor neuron loss. Treatment of EAE mice with the CNS-permeant copper modulating compound CuII(atsm) resulted in recovery of cuproenzyme function, improved myelination and lesion volume, and neuroprotection. These findings support targeting copper perturbations as a therapeutic strategy for MS with CuII(atsm) showing initial promise.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Neurotherapeutics Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Neurotherapeutics Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos