Chair: Natalia Malek (Wroclaw University of Science and Technology, Wroclaw, Poland)

Symposium 15: Bridging Autoimmunity and Neurodegeneration: Immune Cells in Action

This symposium focuses on the immune mechanisms underlying autoimmune disorders and their impact on neurodegeneration. Presentations will discuss the roles of B cells, T cells, and macrophages in diseases like GABAA receptor autoimmune encephalitis and Anti-IgLON5 disease, paving the way for innovative clinical strategies and interventions.


Bart Eggen, Faculty of Medical Sciences, University of Groningen, Groningen, Netherlands

The Shapes and States of CNS Macrophages in the Healthy and Diseased Human Brain

Microglia exhibit a unique transcriptional profile that reflects their role as macrophages in the central nervous system (CNS). These cells are often key contributors to the initiation and progression of neuroinflammatory and neurodegenerative diseases. Recent studies have shed light on the changes microglia undergo during development and in various CNS conditions. Advances in single-cell and spatial profiling technologies have enabled detailed phenotyping of individual microglia. This discussion will focus on the heterogeneity of microglia and their critical roles in human CNS development, maintaining homeostasis, and contributing to neuroinflammatory diseases.

References:
1. Alsema AM, et al. Decoding spatial gene activity changes in multiple sclerosis lesion progression, Nature Neuroscience, in press
2. Eggen BJL, How the cGAS-STING system links inflammation and cognitive decline. Nature., 2023. doi: 10.1038/d41586-023-02240-1


Maarten Titulaer, Erasmus MC, Erasmus University Rotterdam, Rotterdam, Netherlands

Integrating Single-Cell Sequencing and OLINK Proteomics in Understanding IgLON5 Disease

Recent research on IgLON5 disease has utilized single-cell sequencing and OLINK proteomics to gain insights into its pathophysiology. Single-cell analysis enables the characterization of individual immune and neuronal cell populations, revealing the heterogeneity of responses associated with IgLON5 antibodies. OLINK technology provides a comprehensive profiling of proteins in the cerebrospinal fluid, identifying potential biomarkers linked to disease progression and severity. Together, these advanced techniques have facilitated a deeper understanding of the immune and neurodegenerative processes underlying IgLON5 disease. This integrated approach may pave the way for the development of targeted therapies and improved diagnostic strategies for affected patients.

References:
1. Graus F, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol., 2016. doi: 10.1016/S1474-4422(15)00401-9
2. Gelpi E, et al. Neuropathological spectrum of anti-IgLON5 disease and stages of brainstem tau pathology: updated neuropathological research criteria of the disease-related tauopathy. Acta Neuropathol., 2024. doi: 10.1007/s00401-024-02805-y

A disclosure of any potential conflicts of interest: Dr. Titulaer was supported by an Erasmus MC fellowship and received funding from various sources, including the Netherlands Organization for Scientific Research (NWO, Veni), ZonMw (Memorabel program), the Dutch Epilepsy Foundation, Dioraphte, E-RARE JTC 2018, the European Joint Program on Rare Diseases (EJP-RD), and the Erasmus Trustfonds. He has filed a patent for methods and devices related to neurological disorders and cancer on behalf of Erasmus MC. Dr. Titulaer also received research funds for serving on advisory boards for Horizon Therapeutics/Amgen and Argenx, consulting for Guidepoint Global LLC and UCB, and an unrestricted grant from Euroimmun AG and CSL Behring. Additionally, he receives royalties from UpToDate Inc.


Agnieszka Zabłocka, Hirszfeld Institute of Immunology and Experimental Therapy PAS, Wroclaw, Poland

Protease Inhibitors in Neurodegenerative Diseases: Investigating Ovocystatin’s Role in Preventing Protein Aggregation

Aggregation of amyloid β (Aβ) peptides in the brain is associated with neurotoxicity and is considered a primary contributor to Alzheimer’s disease (AD) pathogenesis. Therefore, inhibiting Aβ peptide aggregation represents a promising therapeutic and preventative strategy for AD. This study investigates the anti-aggregative properties of ovocystatin, a cysteine protease inhibitor derived from egg white, on Aβ42 fibril formation in vitro. Inhibition was assessed through Thioflavin-T (ThT) fluorescence assays, circular dichroism (CD) spectroscopy, and transmission electron microscopy (TEM). The findings indicate that ovocystatin effectively inhibits Aβ42 fibril formation and reduces oligomer toxicity in PC12 cells, supporting its potential as a therapeutic candidate for AD.

References:
1. Stańczykiewicz B, et al. Effect of Ovocystatin on Amyloid β 1-42 Aggregation-In Vitro Studies. Int J Mol Sci., 2023. doi: 10.3390/ijms24065433


Natalia Malek, Wroclaw University of Science and Technology, Wroclaw, Poland

Application of Activity-Based Probes for Visualizing Alterations in Proteasome and Immunoproteasome Function in Neuroinflammation

Proteostasis is essential for the regulation of protein synthesis, folding, and degradation within cells. When this balance is disrupted, it can lead to neurodegenerative diseases such as Alzheimer’s and Parkinson’s, which are marked by protein inclusions. Dysregulation often stems from altered catalytic activity of the 20S proteasome and immunoproteasome subunits. This study aimed to investigate how inflammation affects the activity of these subunits in human microglial cell lines. Our methods included transcriptomic analysis via RT-qPCR, proteomic analysis using Western blotting, and activity profiling with activity-based probes (ABPs). Results indicated increased expression of β1 and β5 subunits, along with altered activity levels, highlighting potential therapeutic targets for neurodegenerative conditions.

References:
1. Malek N, et al. Targeting Microglial Immunoproteasome: A Novel Approach in Neuroinflammatory-Related Disorders. ACS Chem Neurosci., 2024.
doi: 10.1021/acschemneuro.4c00099
2. Gladysz R, et al. Investigation of the P1′ and P2′ sites of IQF substrates and their selectivity toward 20S proteasome subunits. Biol Chem., 2022.
doi: 10.1515/hsz-2022-0261

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