Related Experiment Video
Updated: May 21, 2026
08:51
Cerebellar Regional Dissection for Molecular Analysis
Published on: December 5, 2020
Synaptophysin autoantibodies mediate synaptic dysfunction in cerebellar ataxia.
Samantha Ho1, Hoi Kiu Wong2, Dorina Shqau2
1Institute of Clinical Neuroimmunology, LMU University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, Germany; Biomedical Center, Medical Faculty, Ludwig-Maximilians-Universität München, 82152 Planegg-Martinsried, Germany; Graduate School of Systemic Neuroscience, Ludwig-Maximilians-Universität München, 82152 Planegg-Martinsried, Germany.
Cell Reports. Medicine
|May 19, 2026
Summary
Researchers identified synaptophysin (SYP) as a new target for immune-mediated cerebellar ataxias (CAs). SYP antibodies in patients disrupt synaptic function, offering new diagnostic and therapeutic avenues for seronegative CA cases.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Cerebellar ataxias (CAs) have diverse origins, including immune-mediated causes.
- Many CA patients lack identifiable autoantibodies, complicating diagnosis and treatment.
- Identifying novel autoantigens is crucial for understanding and managing these conditions.
Purpose of the Study:
- To identify novel autoantigens in cerebellar ataxias (CAs).
- To investigate the role of synaptophysin (SYP) as a potential autoantigen in CA.
- To explore the functional consequences of SYP autoantibodies on synaptic function.
Main Methods:
- Serum IgG staining on primate cerebellar tissue.
- Human protein array and cell-based assays (CBA) for autoantibody detection.
- Experiments using human induced pluripotent stem cell (iPSC)-derived neurons and multi-electrode arrays.
Main Results:
- Synaptophysin (SYP) was identified as an autoantigen in two patients with CA and synaptic reactivity.
- Patient-derived SYP antibodies caused SYP accumulation at the presynaptic membrane in neurons.
- Both patient IgG and SYP monoclonal antibodies reduced neuronal network activity.
Conclusions:
- Synaptophysin (SYP) is a newly identified autoantigen in a subset of cerebellar ataxia (CA) patients.
- SYP autoantibodies contribute to synaptic dysfunction through mechanisms affecting presynaptic vesicle exposure and neuronal activity.
- This discovery aids in stratifying CA patients and suggests potential therapeutic targets.
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