RNA Splicing Dysregulation in Parkinson’s Disease
Maria Giusy Brunoa, Giacomo Menichettia, Angela Valentinoa, Aqsa Javaida, Francesca Belpinatia, Alessandra Ruggieroa, Maria Teresa Valentia, Giovanna Paoloneb, Fabio Cavalierec, Elisabetta Trabettia, Maria Grazia Romanellia✉, Cristina Bombieria✉
- aDepartment of Neuroscience, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy
- bDepartment of Diagnostics and Public Health, Section of Pharmacology, University of Verona, 37134 Verona, Italy
- cAchucarro Basque Center for Neuroscience, The Basque Biomodels Platform for Human Research (BBioH), 48940 Leioa, Spain
- ✉Corresponding author
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Abstract
Genetic mutations, altered RNA regulation, and protein aggregation are the main hallmarks of Parkinson’s disease (PD), a neurodegenerative disorder. Investigation into the molecular basis of the disease revealed that post-transcriptional regulation, specifically RNA processing, contributes to neuronal vulnerability in PD. Alterations in alternative splicing affecting genes involved in neuronal function and cellular homeostasis have been reported in PD, including SNCA, LRRK2, MAPT, PRKN, and BIN1. These alterations impact central neuronal pathways, including cytoskeletal maintenance, mitochondrial function, synaptic activity, oxidative stress, and intracellular trafficking. This review aims to provide an overview of alternative splicing in key PD gene transcripts, with a focus on their roles in pathogenesis and disease progression. Emerging data suggest that dysregulation of RNA binding proteins (RBPs) may influence RNA processing in PD. We will examine current evidence on the RNA regulatory networks in PD, highlighting the role of transcript isoforms and RBPs in neuronal dysfunction. Finally, we will discuss emerging experimental models such as 3D-brain organoids that offer new opportunities to investigate splicing regulation.
TL;DRCurrent evidence on the RNA regulatory networks in PD is examined, highlighting the role of transcript isoforms and RBPs in neuronal dysfunction and emerging data suggest that dysregulation of RNA binding proteins (RBPs) may influence RNA processing in PD. (Semantic Scholar)