ArticleThe Journal of clinical investigation2015
Purkinje neuron Ca2+ influx reduction rescues ataxia in SCA28 model.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 81 citations in OpenAlex.
- Cerebroprotective potential of ceftriaxone against cadmium chloride-induced cerebral inflammatory changes and oxidative insult.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Cerebellar deep brain stimulation rescues Purkinje cell mitochondrial density in a genetic mouse model of cerebellar ataxia.Brain research bulletin · 2026Article
- Plasma membrane calcium ATPases and cerebellar pathology: what's the role in the ataxia?Biology direct · 2025Review
- Autosomal Recessive Cerebellar Ataxias: Translating Genes to Therapies.Annals of neurology · 2025Review
- Quality control at the powerhouse: mitochondrial proteostasis dysfunction and disease.Biochemical Society transactions · 2025Article
- Compound heterozygous mutation of AFG3L2 causes autosomal recessive spinocerebellar ataxia through mitochondrial impairment and MICU1 mediated CaScience China. Life sciences · 2025Article
- Retinal degeneration in spinocerebellar ataxia type 7: an overview of the current knowledge.Arquivos brasileiros de oftalmologia · 2025Review
- Neuronal Nitric Oxide Synthase Regulates Cerebellar Parallel Fiber Slow EPSC in Purkinje Neurons by Modulating STIM1-Gated TRPC3-Containing Channels.Cerebellum (London, England) · 2024Article
- Toll-like receptor 4 deficiency in Purkinje neurons drives cerebellar ataxia by impairing the BK channel-mediated after-hyperpolarization and cytosolic calcium homeostasis.Cell death & disease · 2024Article
- Multifaceted Roles of AFG3L2, a Mitochondrial ATPase in Relation to Neurological Disorders.Molecular neurobiology · 2024Review
- Sustained OMA1-mediated integrated stress response is beneficial for spastic ataxia type 5.Brain : a journal of neurology · 2024Article
- Review
- Restoring calcium homeostasis in Purkinje cells arrests neurodegeneration and neuroinflammation in the ARSACS mouse model.JCI insight · 2023Article
- Targeting Ion Channels and Purkinje Neuron Intrinsic Membrane Excitability as a Therapeutic Strategy for Cerebellar Ataxia.Life (Basel, Switzerland) · 2023Review
- Preserving and enhancing mitochondrial function after stroke to protect and repair the neurovascular unit: novel opportunities for nanoparticle-based drug delivery.Frontiers in cellular neuroscience · 2023Review
- Viewpoint: spinocerebellar ataxias as diseases of Purkinje cell dysfunction rather than Purkinje cell loss.Frontiers in molecular neuroscience · 2023Review
- Regulation of mitochondrial proteostasis by the proton gradient.The EMBO journal · 2022Article
- Review
- ATAD3A has a scaffolding role regulating mitochondria inner membrane structure and protein assembly.Cell reports · 2021Article
- A Mitocentric View of the Main Bacterial and Parasitic Infectious Diseases in the Pediatric Population.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
Spinocerebellar ataxia type 28 (SCA28) is a neurodegenerative disease caused by mutations of the mitochondrial protease AFG3L2. The SCA28 mouse model, which is haploinsufficient for Afg3l2, exhibits a progressive decline in motor function and displays dark degeneration of Purkinje cells (PC-DCD) of mitochondrial origin. Here, we determined that mitochondria in cultured Afg3l2-deficient PCs ineffectively buffer evoked Ca²⁺ peaks, resulting in enhanced cytoplasmic Ca²⁺ concentrations, which subsequently triggers PC-DCD. This Ca²⁺-handling defect is the result of negative synergism between mitochondrial depolarization and altered organelle trafficking to PC dendrites in Afg3l2-mutant cells. In SCA28 mice, partial genetic silencing of the metabotropic glutamate receptor mGluR1 decreased Ca²⁺ influx in PCs and reversed the ataxic phenotype. Moreover, administration of the β-lactam antibiotic ceftriaxone, which promotes synaptic glutamate clearance, thereby reducing Ca²⁺ influx, improved ataxia-associated phenotypes in SCA28 mice when given either prior to or after symptom onset. Together, the results of this study indicate that ineffective mitochondrial Ca²⁺ handling in PCs underlies SCA28 pathogenesis and suggest that strategies that lower glutamate stimulation of PCs should be further explored as a potential treatment for SCA28 patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.