Age-related neurodegenerative diseases, such as Alzheimer’s, are an increasing burden on society. While immune signaling contributes to the pathogenesis of these diseases, the nature of the immune genes involved is largely unknown. We aim to identify immune genes that contribute to the pathogenesis of neurodegenerative diseases and to alleviate symptoms by manipulating the activity of these genes.
We focus on two disease models:
- SCA3: expansion of a polyglutamine stretch causes aggregation of this protein and neurotoxicity.
- Alzheimer: in brains of patients extracellular aggregates of Abeta peptides are found. These peptides are neurotoxic.
We have carried out a genetic screen in Drosophila (fruit flies), using expression of human SCA3 in the Drosophila eye. We examined involvement of (1) brain-resident immune cells (astrocytes and microglia) and (2) peripheral immune cells. We are further analyzing the identified genes (both enhancers of suppressors of SCA3) and testing them in the Alzheimer model.
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Figure: Identification of immune genes involved in neurodegeneration. Expression of expanded SCA3 (SCA3 78Q) in Drosophila eyes results in a degenerative phenotype. We identified enhancers as well as suppressors of this phenotype, using RNA interference in immune cells.
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