ArticleActa neuropathologica2014
Paraneoplastic CDR2 and CDR2L antibodies affect Purkinje cell calcium homeostasis.
Article in Acta neuropathologica, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- What is the significance of onconeural antibodies for psychiatric symptomatology? A systematic review.BMC psychiatry · 2017Pooled it
- CDR2 is a dynein adaptor recruited by kinectin to regulate ER sheet organization.The Journal of cell biology · 2025Article
- Cell-free DNA integrity and complement C4d as novel liquid biopsy biomarkers for paraneoplastic and non-paraneoplastic autoimmune encephalitis.Frontiers in immunology · 2025Article
- Roles of CDR2 and CDR2L in Anti-Yo Paraneoplastic Cerebellar Degeneration: A Literature Review.International journal of molecular sciences · 2024Review
- Multi-omics profiling reveals dysregulated ribosome biogenesis and impaired cell proliferation following knockout of CDR2L.BMC cancer · 2024Article
- A Pilot Study to Develop Paraneoplastic Cerebellar Degeneration Mouse Model.Cerebellum (London, England) · 2024Article
- Development and Optimization of a Multilayer Rat Purkinje Neuron Culture.Cerebellum (London, England) · 2024Article
- The Discovery of Anti-Yo (Anti-PCA1) Antibody in Patients with Paraneoplastic Cerebellar Degeneration: Opening a Window into Autoimmune Neurological Disease.Cerebellum (London, England) · 2023Article
- Inositol 1,4,5-trisphosphate receptor type 1 autoantibody (ITPR1-IgG/anti-Sj)-associated autoimmune cerebellar ataxia, encephalitis and peripheral neuropathy: review of the literature.Journal of neuroinflammation · 2022Review
- Paraneoplastic Cerebellar Degeneration With P/Q-VGCC vs Yo Autoantibodies.Neurology(R) neuroimmunology & neuroinflammation · 2022Article
- Acute Cerebellar Inflammation and Related Ataxia: Mechanisms and Pathophysiology.Brain sciences · 2022Review
- A Breakdown of Immune Tolerance in the Cerebellum.Brain sciences · 2022Review
- 16p12.1 Deletion Orthologs are Expressed in Motile Neural Crest Cells and are Important for Regulating Craniofacial Development inFrontiers in genetics · 2022Article
- Understanding the genomic architecture of clinical mastitis in3 Biotech · 2021Article
- Paraneoplastic cerebellar degeneration in platinum-responsive endometrial cancer: A case report and review of literature.Gynecologic oncology reports · 2021Review
- Paraneoplastic neurological syndrome: an evolving story.Neuro-oncology practice · 2021Review
- Paraneoplastic Cerebellar Degeneration: The Importance of Including CDR2L as a Diagnostic Marker.Neurology(R) neuroimmunology & neuroinflammation · 2021Article
- Paraneoplastic and Other Autoimmune Encephalitides: Antineuronal Antibodies, T Lymphocytes, and Questions of Pathogenesis.Frontiers in neurology · 2021Review
- Localization of CDR2L and CDR2 in paraneoplastic cerebellar degeneration.Annals of clinical and translational neurology · 2020Article
- Paraneoplastic Diseases of the Central Nervous System.F1000Research · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Paraneoplastic cerebellar degeneration (PCD) is characterized by loss of Purkinje cells (PCs) associated with progressive pancerebellar dysfunction in the presence of onconeural Yo antibodies. These antibodies recognize the cerebellar degeneration-related antigens CDR2 and CDR2L. Response to PCD therapy is disappointing due to limited understanding of the neuropathological mechanisms. Here, we report the pathological role of CDR antibodies on the calcium homeostasis in PCs. We developed an antibody-mediated PCD model based on co-incubation of cerebellar organotypic slice culture with human patient serum or rabbit CDR2 and CDR2L antibodies. The CDR antibody-induced pathology was investigated by high-resolution multiphoton imaging and biochemical analysis. Both human and rabbit CDR antibodies were rapidly internalized by PCs and led to reduced immunoreactivity of calbindin D28K (CB) and L7/Pcp-2 as well as reduced dendritic arborizations in the remaining PCs. Washout of the CDR antibodies partially recovered CB immunoreactivity, suggesting a transient structural change in CB calcium-binding site. We discovered that CDR2 and CB co-immunoprecipitate. Furthermore, the expression levels of voltage-gated calcium channel Cav2.1, protein kinase C gamma and calcium-dependent protease, calpain-2, were increased after CDR antibody internalization. Inhibition of these signaling pathways prevented or attenuated CDR antibody-induced CB and L7/Pcp-2 immunoreactivity loss, morphological changes and increased protein expression. These results signify that CDR antibody internalization causes dysregulation of cell calcium homeostasis. Hence, drugs that modulate these events may represent novel neuroprotective therapies that limit the damaging effects of CDR antibodies and prevent PC neurodegeneration.
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Registered trials
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