Alternative splicing and neurological disorders: focus on Parkinson's disease

Alternative splicing (AS) is a fundamental mechanism of gene expression regulation that extremely expands the coding potential of genomes and the cellular transcriptomic and protein diversity. This dynamic and finely-tuned machinery is particularly widespread in the nervous system and is critical for both neuronal development and functions. Alternative splicing defects, therefore, frequently underlie neurological disorders. In this chapter, we will focus on Parkinson's disease (PD), the second most common neurodegenerative disorder worldwide. We will provide a current overview of the impact of alternative splicing on PD by representing the multiple splicing transcripts produced by the major PD-linked genes and their regulation in PD states. Furthermore, we will recapitulate the studies describing global splicing expression changes revealed by whole-genome transcriptomic approaches. We will also summarize the current knowledge about the alternative splicing modulation in PD through non-coding RNAs (miRNA and lcnRNA) molecules. Assessing the role of alternative splicing on PD pathobiology may represent a central step toward an improved understanding of this complex disease.