Roles of lncRNAs in brain development and pathogenesis: Emerging therapeutic opportunities

The human genome is pervasively transcribed, producing a majority of short and long noncoding RNAs (lncRNAs) that can influence cellular programs through a variety of transcriptional and post-transcriptional regulatory mecha- nisms. The brain houses the richest repertoire of long noncoding transcripts, which function at every stage during central nervous system development and homeostasis. An example of functionally relevant lncRNAs is species involved in spatiotemporal organization of gene expression in different brain regions, which play roles at the nuclear level and in transport, translation, and decay of other transcripts in specific neuronal sites. Research in the field has enabled identification of the contributions of specific lncRNAs to certain brain diseases, including Alzheimer's disease, Parkin- son's disease, cancer, and neurodevelopmental disorders, re- sulting in notions of potential therapeutic strategies that target these RNAs to recover the normal phenotype. Here, we summarize the latest mechanistic findings associated with lncRNAs in the brain, focusing on their dysregulation in neurodevelopmental or neurodegenerative disorders, their use as biomarkers for central nervous system (CNS) diseases in vitro and in vivo, and their potential utility for therapeu- tic strategies.