Alternative splicing of mRNA in the molecular pathology of neurodegenerative diseases

Abstract

Alternative splicing (AS) is a post-transcriptional process that occurs in multiexon genes, and errors in this process have been implicated in many human diseases. Until recently, technological limitations prevented AS from being examined at the genome-wide scale. With the advent of new technologies, including exon arrays and next-generation sequencing (NGS) techniques (e.g., RNA-Seq), a higher resolution view of the human transcriptome is now available. This is particularly applicable in the study of neurodegenerative brain diseases (NBDs), such as Alzheimer's disease and Parkinson's disease, because the brain has the greatest amount of alternative splicing of all human tissues. Although many of the AS events associated with these disorders were initially identified using low-throughput methodologies, genome-wide analysis allows for more in-depth studies, marking a new chapter in transcript exploration. In this review, the latest technologies used to study the transcriptome and the AS genes that have been associated with a number of neurodegenerative brain diseases are discussed.