Cerebellar lipid dysregulation in SCA3: A comparative study in patients and mice DOI Creative Commons
Alexandra F. Putka, Varshasnata Mohanty, Stephanie M. Cologna

et al.

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106827 - 106827

Published: Feb. 1, 2025

Spinocerebellar ataxia type 3 (SCA3) is the most common dominantly inherited and belongs to family of nine diseases caused by a polyglutamine expansion in disease-causing protein. In SCA3, ATXN3 causes neuron loss disease-vulnerable brain regions, resulting progressive coordination ultimately death. There are no disease-modifying or preventative treatments for this uniformly fatal disorder. Recent studies demonstrate prominent white matter atrophy microstructural alterations regions SCA3 patients mouse models. However, major constituent - lipids remains understudied SCA3. study, we conducted first unbiased investigation focusing on cerebellum postmortem Liquid chromatography-mass spectrometry uncovered widespread lipid reductions with Lipid downregulation was recapitulated early- mid-stage models including transgenic YACQ84 Knock-in Q300 mice. End-stage mice displayed reduction content, highlighting targets that could benefit from early therapeutic intervention. contrast, Atxn3-Knock-out showed mild upregulation, emphasizing toxic gain-of-function mechanism underlying We conclude significantly altered establish platform continued exploration disease through interactive data visualization websites. Pronounced myelin-enriched suggest dysregulation underlie This study establishes basis future work elucidating mechanistic, biomarker, potential

Language: Английский

Cerebellar lipid dysregulation in SCA3: A comparative study in patients and mice DOI Creative Commons
Alexandra F. Putka, Varshasnata Mohanty, Stephanie M. Cologna

et al.

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106827 - 106827

Published: Feb. 1, 2025

Spinocerebellar ataxia type 3 (SCA3) is the most common dominantly inherited and belongs to family of nine diseases caused by a polyglutamine expansion in disease-causing protein. In SCA3, ATXN3 causes neuron loss disease-vulnerable brain regions, resulting progressive coordination ultimately death. There are no disease-modifying or preventative treatments for this uniformly fatal disorder. Recent studies demonstrate prominent white matter atrophy microstructural alterations regions SCA3 patients mouse models. However, major constituent - lipids remains understudied SCA3. study, we conducted first unbiased investigation focusing on cerebellum postmortem Liquid chromatography-mass spectrometry uncovered widespread lipid reductions with Lipid downregulation was recapitulated early- mid-stage models including transgenic YACQ84 Knock-in Q300 mice. End-stage mice displayed reduction content, highlighting targets that could benefit from early therapeutic intervention. contrast, Atxn3-Knock-out showed mild upregulation, emphasizing toxic gain-of-function mechanism underlying We conclude significantly altered establish platform continued exploration disease through interactive data visualization websites. Pronounced myelin-enriched suggest dysregulation underlie This study establishes basis future work elucidating mechanistic, biomarker, potential

Language: Английский

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