A5060819240- Genetics and Neurodevelopmental Disorders
- Autism Spectrum Disorder Research
- Chromatin Remodeling and Cancer
- Genomic variations and chromosomal abnormalities
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Retinoids in leukemia and cellular processes
- Estrogen and related hormone effects
- Tryptophan and brain disorders
- Hormonal Regulation and Hypertension
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Endoplasmic Reticulum Stress and Disease
- Family and Disability Support Research
- Congenital heart defects research
- Cannabis and Cannabinoid Research
- Genetic and Kidney Cyst Diseases
- Protein Degradation and Inhibitors
- Hedgehog Signaling Pathway Studies
- Nuclear Structure and Function
- Acute Myeloid Leukemia Research
University of Insubria
2012-2022
Expression Génétique Microbienne
1999
Rett syndrome (RTT) is a severe neurodevelopmental disorder almost exclusively affecting females and characterized by wide spectrum of clinical manifestations. Most patients affected classic RTT smaller percentage with the milder form 'preserved speech variant' have either point mutations or deletions/duplications in MECP2 gene. Recently, CDKL5 gene, coding for putative kinase, been found female phenotype overlapping that RTT. Here, we report two early seizure variant RTT, bearing novel...
Nuclear localization of the Extradenticle (EXD) and PBX1 proteins is regionally restricted during Drosophila mammalian development. We studied subcellular EXD, PBX, their partners Homothorax (HTH) PREP1, in different cell contexts. HTH PREP1 are cytoplasmic require association with EXD/PBX for nuclear localization. EXD murine fibroblasts but not Schneider cells, which they actively exported to cytoplasm. Coexpression HTH/PREP1 causes heterodimers both propose that heterodimerization HTH/PREP...
Mutations in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified patients with Rett syndrome (RTT), West syndrome, and infantile spasms, sharing common feature of mental retardation early seizures. CDKL5 is a rather uncharacterized kinase, but its involvement RTT seems to be explained by fact that it works upstream MeCP2, main cause syndrome. To understand role this kinase for nervous system functions address if molecular mechanisms are involved regulating...
Mutations in the X-linked Cyclin-Dependent Kinase-Like 5 gene (CDKL5) cause early onset infantile spasms and subsequent severe developmental delay affected children. Deleterious mutations have been reported to occur throughout CDKL5 coding region. Several studies point a complex structure terms of exon usage transcript expression. Improvements molecular diagnosis more extensive research into neurobiology pathophysiology disorders necessitate an updated analysis gene. In this study, we...
MeCP2 is associated with several neurological disorders; of which, Rett syndrome undoubtedly represents the most frequent. Its molecular roles, however, are still unclear, and data from animal models often describe adult, symptomatic stages, while functions during embryonic development remain elusive. We pattern timing Mecp2 expression in neocortex highlighting its low but consistent virtually all cells show unexpected occurrence transcriptional defects null samples at a stage largely...
In the last years, X-linked cyclin-dependent kinase-like 5 (CDKL5) gene has been associated with epileptic encephalopathies characterized by early onset of intractable epilepsy, severe developmental delay, autistic features, and often development Rett syndrome-like features. Still, role CDKL5 in neuronal functions is not fully understood. By way a yeast two hybrid screening we identified interaction shootin1, brain specific protein acting as determinant axon formation during polarization. We...
Background:Recent evidence suggests that 2-week treatment with the non-psychotomimetic cannabinoid cannabidivarin (CBDV) could be beneficial towards neurological and social deficits in early symptomatic Mecp2 mutant mice, a model of Rett syndrome (RTT). Aim:The aim this study was to provide further insights into efficacy CBDV Mecp2-null mice using lifelong schedule (from 4 9 weeks age) evaluate its effect on recognition memory defects both advanced stages phenotype progression. Methods:CBDV...
Mutations in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been shown to cause severe neurodevelopmental disorders including infantile spasms, encephalopathy, West-syndrome and an early-onset variant of Rett syndrome. CDKL5 is a serine/threonine kinase whose involvement syndrome can be inferred by its ability directly bind mediate phosphorylation MeCP2. However, it remains elucidated how exerts function. Here, we report that localizes specific nuclear foci referred as...
Mutations in MECP2 cause several neurological disorders of which Rett syndrome (RTT) represents the best-defined condition. Although mainly working as a transcriptional repressor, MeCP2 is multifunctional protein revealing activities, involvement RTT remains obscure. Besides being localized nucleus, associates with centrosome, an organelle from primary cilia originate. Primary function "sensory antennae" protruding most cells, and link between mental illness has recently been reported. We...
Rett syndrome is a severe neurodevelopmental disorder mainly caused by mutations in the transcriptional regulator MeCP2. Although there no effective therapy for syndrome, recently discovered disease reversibility mice suggests that are therapeutic possibilities. Identification of MeCP2 targets or modifiers phenotype can facilitate design curative strategies. To identify possible novel interactors, we exploited bioinformatic approach and selected Ying Yang 1 (YY1) as an interesting candidate....
Rett syndrome (RTT) is an autism spectrum disorder mainly caused by mutations in the X-linked MECP2 gene and affecting roughly 1 out of 10.000 born girls. Symptoms range severity include stereotypical movement, lack spoken language, seizures, ataxia severe intellectual disability. Notably, muscle tone generally abnormal RTT girls women Mecp2-null mouse model constitutively reflects this disease feature. We hypothesized that MeCP2 might physiologically contribute to its development and/or...
CDKL5 deficiency disorder (CDD) is a rare X-linked neurodevelopmental that characterised by early-onset seizures, intellectual disability, gross motor impairment, and autistic-like features. CDD caused mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene encodes serine/threonine kinase with predominant expression brain. Loss of causes alterations vitro vivo, including defective dendritic arborisation spine maturation, which most likely underlie cognitive defects autistic features...
Mutations in the X-linked CDKL5 (cyclin-dependent kinase-like 5) gene have been associated with several forms of neurodevelopmental disorders, including atypical Rett syndrome, autism spectrum and early infantile epileptic encephalopathy. Accordingly, loss mice results autistic-like features impaired neuronal communication. Although biological functions remain largely unknown, recent pieces evidence suggest that is involved plasticity. Herein, we show that, at all stages development,...
CDKL5 is a protein kinase that plays key role for neuronal functions as testified by the onset of complex dysfunctions in patients with genetic lesions CDKL5. Here we identify novel interactor CDKL5, IQGAP1, fundamental regulator cell migration and polarity. In accordance functional this interaction, depletion impairs impedes localization IQGAP1 at leading edge. Moreover, demonstrate required to form its effectors, Rac1 microtubule plus end tracking CLIP170. These defects eventually impact...
Abstract The cyclin-dependent kinase-like 5 ( CDKL5 ) gene has been associated with rare neurodevelopmental disorders characterized by the early onset of seizures and intellectual disability. protein is widely expressed in most tissues cells both nuclear cytoplasmic localization. In post-mitotic neurons mainly involved dendritic arborization, axon outgrowth, spine formation while proliferating its function still largely unknown. Here, we report that localizes at centrosome midbody cells....
MECP2 mutations cause a number of neurological disorders which Rett syndrome (RTT) represents the most thoroughly analysed condition. Many Mecp2 mouse models have been generated through years; their validity is demonstrated by presence broad spectrum phenotypes largely mimicking those manifested RTT patients. These models, between C57BL/6 Mecp2tm1.1Bird strain probably used, enabled to disclose much roles Mecp2. However, small litters with little viability and poor maternal care hamper...
Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene cause a complex neurological disorder, characterized by infantile seizures, impairment of cognitive and motor skills autistic features. Loss Cdkl5 mice affects dendritic spine maturation dynamics but underlying molecular mechanisms are still far from fully understood. Here we show that deficiency primary hippocampal neurons leads to deranged expression alpha-amino-3-hydroxy-5-methyl-4-iso-xazole propionic acid receptors...