TY - JOUR T1 - Mechanisms of Neuronal Alternative Splicing and Strategies for Therapeutic Interventions JF - The Journal of Neuroscience JO - J. Neurosci. SP - 8193 LP - 8199 DO - 10.1523/JNEUROSCI.1149-19.2019 VL - 39 IS - 42 AU - Eduardo Javier Lopez Soto AU - Michael J. Gandal AU - Thomas Gonatopoulos-Pournatzis AU - Elizabeth A. Heller AU - Diou Luo AU - Sika Zheng Y1 - 2019/10/16 UR - http://www.jneurosci.org/content/39/42/8193.abstract N2 - Many cellular and physiological processes are coordinated by regulatory networks that produce a remarkable complexity of transcript isoforms. In the mammalian nervous system, alternative pre-mRNA splicing generates functionally distinct isoforms that play key roles in normal physiology, supporting development, plasticity, complex behaviors, and cognition. Neuronal splicing programs controlled by RNA-binding proteins, are influenced by chromatin modifications and can exhibit neuronal subtype specificity. As highlighted in recent publications, aberrant alternative splicing is a major contributor to disease phenotypes. Therefore, understanding the underlying mechanisms of alternative splicing regulation and identifying functional splicing isoforms with critical phenotypic roles are expected to provide a comprehensive resource for therapeutic development, as illuminated by recent successful interventions of spinal muscular atrophy. Here, we discuss the latest progress in the study of the emerging complexity of alternative splicing mechanisms in neurons, and how these findings inform new therapies to correct and control splicing defects. ER -