ArticleMovement disorders : official journal of the Movement Disorder Society2020
In Vivo Molecular Signatures of Cerebellar Pathology in Spinocerebellar Ataxia Type 3.
Article in Movement disorders : official journal of the Movement Disorder Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 34 citations in OpenAlex.
- From equilibrium to dynamic metabolic imaging: the evolving role of magnetic resonance spectroscopic imaging in neurodegenerative disorders.Journal of translational medicine · 2026Review
- Article
- Oligodendrocyte dysfunction contributes to motor deficits and Purkinje cell axonopathy in spinocerebellar ataxia type 1.The Journal of clinical investigation · 2026Article
- Rad23b exacerbates pathological aggregates through disrupting proteasome functions in Spinocerebellar ataxia type 3.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Brain atrophy staging in spinocerebellar ataxia type 3 for clinical prognosis and trial enrichment.EBioMedicine · 2026Article
- Ataxin-3 Overexpression via Adeno-associated Viral Vector Injection in the Primate Cerebellum: A Novel Model of Spinocerebellar Ataxia Type 3.Experimental neurobiology · 2025Article
- Long-read sequencing identifies ATXN3 repeat expansions, and transcriptomics reveals disease progression biomarkers and druggable targets for spinocerebellar ataxia type 3.BMC neurology · 2025Article
- Treatment of neurological pathology and inflammation in Machado-Joseph disease through in vivo self-assembled siRNA.Brain : a journal of neurology · 2025Article
- Cerebellar lipid dysregulation in SCA3: A comparative study in patients and mice.Neurobiology of disease · 2025Article
- ASOs are an effective treatment for disease-associated oligodendrocyte signatures in premanifest and symptomatic SCA3 mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Longitudinal single-cell transcriptional dynamics throughout neurodegeneration in SCA1.Neuron · 2024Article
- Widespread alternative splicing dysregulation occurs presymptomatically in CAG expansion spinocerebellar ataxias.Brain : a journal of neurology · 2024Article
- Article
- Antisense Oligonucleotide Silencing Reverses Abnormal Neurochemistry in Spinocerebellar Ataxia 3 Mice.Annals of neurology · 2023Article
- Blood levels of neurofilament light are associated with disease progression in a mouse model of spinocerebellar ataxia type 3.Disease models & mechanisms · 2023Article
- Blood neurofilament light chain levels are associated with disease progression in a transgenic SCA3 mouse model.bioRxiv : the preprint server for biology · 2023Article
- Myelinating Glia: Potential Therapeutic Targets in Polyglutamine Spinocerebellar Ataxias.Cells · 2023Review
- Disease-associated oligodendrocyte signatures are spatiotemporally dysregulated in spinocerebellar ataxia type 3.Frontiers in neuroscience · 2023Article
- Article
- Brain structural abnormalities in the preclinical stage of Machado-Joseph disease/spinocerebellar ataxia type 3 (MJD/SCA3): evaluation by MRI morphometry, diffusion tensor imaging and neurite orientation dispersion and density imaging.Journal of neurology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundNo treatment exists for the most common dominantly inherited ataxia Machado-Joseph disease, or spinocerebellar ataxia type 3 (SCA3). Successful evaluation of candidate therapeutics will be facilitated by validated noninvasive biomarkers of disease pathology recapitulated by animal models.
objectiveWe sought to identify shared in vivo neurochemical signatures in two mouse models of SCA3 that reflect the human disease pathology.
methodsCerebellar neurochemical concentrations in homozygous YACMJD84.2 (Q84/Q84) and hemizygous CMVMJD135 (Q135) mice were measured by in vivo magnetic resonance spectroscopy at 9.4 tesla. To validate the neurochemical biomarkers, levels of neurofilament medium (NFL; indicator of neuroaxonal integrity) and myelin basic protein (MBP; indicator of myelination) were measured in cerebellar lysates from a subset of mice and patients with SCA3. Finally, NFL and MBP levels were measured in the cerebellar extracts of Q84/Q84 mice upon silencing of the mutant ATXN3 gene.
resultsBoth Q84/Q84 and Q135 mice displayed lower N-acetylaspartate than wild-type littermates, indicating neuroaxonal loss/dysfunction, and lower myo-inositol and total choline, indicating disturbances in phospholipid membrane metabolism and demyelination. Cerebellar NFL and MBP levels were accordingly lower in both models as well as in the cerebellar cortex of patients with SCA3 than controls. Importantly, N-acetylaspartate and total choline correlated with NFL and MPB, respectively, in Q135 mice. Long-term sustained RNA interference (RNAi)-mediated reduction of ATXN3 levels increased NFL and MBP in Q84/Q84 cerebella.
conclusionsN-acetylaspartate, myo-inositol, and total choline levels in the cerebellum are candidate biomarkers of neuroaxonal and oligodendrocyte pathology in SCA3, aspects of pathology that are reversible by RNAi therapy. © 2020 International Parkinson and Movement Disorder Society.
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