한규만 교수

Proper neurological function in humans requires precise control of levels of the epigenetic regulator methyl CpG-binding protein 2 (MeCP2). MeCP2 protein levels are low in fetal brains, where the predominant MECP2 transcripts have an unusually long 3' untranslated region (UTR). Here, we show that miR-483-5p, an intragenic microRNA of the imprinted IGF2, regulates MeCP2 levels through a human-specific binding site in the MECP2 long 3' UTR. We demonstrate the inverse correlation of miR-483-5p and

Silencing of fragile X mental retardation 1 (FMR1) gene and loss of fragile X mental retardation protein (FMRP) cause fragile X syndrome (FXS), a genetic disorder characterized by intellectual disability and autistic behaviors. FMRP is an mRNA-binding protein regulating neuronal translation of target mRNAs. Abnormalities in actin-rich dendritic spines are major neuronal features in FXS, but the molecular mechanism and identity of FMRP targets mediating this phenotype remain largely unknown. Cyto

Mania causes symptoms of hyperactivity, impulsivity, elevated mood, reduced anxiety and decreased need for sleep, which suggests that the dysfunction of the striatum, a critical component of the brain motor and reward system, can be causally associated with mania. However, detailed molecular pathophysiology underlying the striatal dysfunction in mania remains largely unknown. In this study, we aimed to identify the molecular pathways showing alterations in the striatum of SH3 and multiple ankyri

Variants of the SH3 and multiple ankyrin repeat domain 3 (<i>SHANK3</i>) gene, encoding excitatory postsynaptic core scaffolding proteins, are causally associated with numerous neurodevelopmental and neuropsychiatric disorders, including autism spectrum disorder (ASD), bipolar disorder, intellectual disability, and schizophrenia (SCZ). Although detailed synaptic changes of various <i>Shank3</i> mutant mice have been well characterized, broader downstream molecular changes, including direct and i

Recent molecular genetic studies have identified 100s of risk genes for various neurodevelopmental and neuropsychiatric disorders. As the number of risk genes increases, it is becoming clear that different mutations of a single gene could cause different types of disorders. One of the best examples of such a gene is <i>SHANK3</i>, which encodes a core scaffold protein of the neuronal excitatory post-synapse. Deletions, duplications, and point mutations of <i>SHANK3</i> are associated with autism

BACKGROUND The effect of foot orthoses in terms of kinematics and kinetics during walking could be affected on different geometrical designs. Therefore, the purpose of this study was to compare the biomechanical and clinical effects of 3 different insoles on rearfoot motion (RFM) and ankle joint moment parameters. MATERIAL AND METHODS Twenty eight university students with flexible flatfoot were recruited for this study, and each participant was asked to wear 3 different insoles: normal insole wi

The SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins are core organizers of the postsynaptic density in neuronal excitatory synapses, and their defects cause various neurodevelopmental and neuropsychiatric disorders. Mechanistically, Shank3 directly and indirectly interacts with hundreds of synaptic proteins with diverse functions and potentially exerts its regulatory roles in synaptic development and function via these interactors. However, Shank3-dependent regulation of synaptic abu

Recent molecular genetic studies have suggested that two members of the cytoplasmic FMR1-interacting protein (<i>CYFIP</i>) gene family, <i>CYFIP1</i> and <i>CYFIP2</i>, are causally associated with several brain disorders. However, the clinical features of individuals with <i>CYFIP1</i> and <i>CYFIP2</i> variants are quite different. In addition, null mice for either <i>Cyfip1</i> or <i>Cyfip2</i> are lethal, indicating that these two genes cannot compensate for each other in vivo. Although the

Cytoplasmic FMR1-interacting protein 2 (CYFIP2) is a key component of the WAVE regulatory complex (WRC) which regulates actin polymerization and branching in diverse cellular compartments. Recent whole exome sequencing studies identified <i>de novo</i> hotspot variants in <i>CYFIP2</i> from patients with early-onset epileptic encephalopathy and microcephaly, suggesting that CYFIP2 may have some functions in embryonic brain development. Although perinatal lethality of <i>Cyfip2</i>-null (<i>Cyfip

The cytoplasmic fragile X mental retardation 1 (FMR1)-interacting protein 2 (<i>CYFIP2</i>) gene is associated with epilepsy, intellectual disability (ID), and developmental delay, suggesting its critical role in proper neuronal development and function. CYFIP2 is involved in regulating cellular actin dynamics and also interacts with RNA-binding proteins. However, the adult brain function of CYFIP2 remains unclear because investigations thus far are limited to <i>Cyfip2</i> heterozygous (<i>Cyfi