Ellen Nollen’s lab received Stichting Parkinsonfonds grant

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Suzanne Couzijn and Anna Ainslie from Ellen Nollen’s lab received a grant of € 303.400 from Stichting ParkinsonFonds. Their project “Protecting against alpha-synuclein toxicity at molecular and physiological levels” aims to investigate organismal mechanisms driving alpha-synuclein toxicity, focusing on factors beyond protein aggregation in C. elegans models of Parkinson’s Disease.

Aging is a primary risk factor for neurodegenerative disorders including Parkinson's disease. As individuals age, their cells become less efficient in managing protein homeostasis, leading to an increased likelihood of protein misfolding and aggregation. A hallmark of Parkinson’s disease is the accumulation of alpha-synuclein protein aggregates in affected neurons, a process that is exacerbated by aging. While protein aggregation has been a primary focus of research, recent studies have suggested that other age-related mechanisms may contribute to alpha-synuclein toxicity. Understanding these alternative pathways is crucial for the development of effective therapeutic strategies to combat Parkinson's disease. This study investigates organismal mechanisms driving alpha-synuclein toxicity, focusing on factors beyond protein aggregation. In genome-wide genetic screen in C. elegans, we identified genes that protect against alpha-synuclein toxicity when depleted. These genes comprised several functional classes, including those involved in protein metabolism. This study aims to establish pathways by which these toxicity modifiers alter alpha-synuclein toxicity, with a focus on translation regulators and amino-acid metabolism. It also seeks to understand the functional connection between the newly identified modifiers and our previously established tryptophan-metabolism-mediated protection. Results are expected to reveal mechanisms driving alpha-synuclein toxicity, and the role of protein metabolism in this process. This research may contribute to developing interventions to prevent, delay, or stop Parkinson's disease.

More information can be found here (in Dutch): Bijdrage van Stichting ParkinsonFonds

S. Couzijn and A. Ainslie