Search results for "microtubule"

Hippocampal hyperexcitability is modulated by microtubule-active agent: evidence from in vivo and in vitro epilepsy models in the rat

2016

The involvement of microtubule dynamics on bioelectric activity of neurons and neurotransmission represents a fascinating target of research in the context of neural excitability. It has been reported that alteration of microtubule cytoskeleton can lead to profound modifications of neural functioning, with a putative impact on hyperexcitability phenomena. Altogether, in the present study we pointed at exploring the outcomes of modulating the degree of microtubule polymerization in two electrophysiological epileptiform activity in the rat hippocampus. To this aim, we used in vivo Maximal Dentate Activation (MDA) and in vitro hippocampal epileptiform bursting activity (HEBA) paradigms to asse…

A novel GABRB3 variant in Dravet syndrome: Case report and literature review

2020

Abstract Background Mutations in GABRB3 have been identified in subjects with different types of epilepsy and epileptic syndromes, including West syndrome (WS), Dravet syndrome (DS), Lennox‐Gastaut syndrome (LGS), myoclonic‐atonic epilepsy (MAE), and others. Methods and results We herewith report on a girl affected by DS, who has been followed from infancy to the current age of 18 years. Next‐generation sequencing (NGS)‐based genetic testing for multigene analysis of neurodevelopmental disorders identified two likely de novo pathogenic mutations, a missense variant in GABRB3 gene (c.842 C>T; p.Thr281IIe) and a nonsense variant found in BBS4 gene (c.883 C>T; p.Arg295Ter). Conclusion A likely…

Inhibition of cell migration and induction of apoptosis by a novel class II histone deacetylase inhibitor, MCC2344.

2020

Epigenetic modifiers provide a new target for the development of anti-cancer drugs. The eraser histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase that targets various non-histone proteins such as transcription factors, nuclear receptors, cytoskeletal proteins, DNA repair proteins, and molecular chaperones. Therefore, it became an attractive target for cancer treatment. In this study, virtual screening was applied to the MicroCombiChem database with 1162 drug-like compounds to identify new HDAC6 inhibitors. Five compounds were tested in silico and in vitro as HDAC6 inhibitors. Both analyses revealed 1-cyclohexene-1-carboxamide, 2-hydroxy-4,4-dimethyl-N-1-naphthalenyl-6-oxo- (MC…

The MID1 protein is a central player during development and in disease.

2015

Loss-of-function mutations in the MID1 gene cause a rare monogenic disorder, Opitz BBB/G syndrome (OS), which is characterized by malformations of the ventral midline. The MID1 gene encodes the MID1 protein, which assembles a large microtubule-associated protein complex. Intensive research over the past several years has shed light on the function of the MID1 protein as a ubiquitin ligase and regulator of mTOR signalling and translational activator. As a central player in the cell MID1 has been implicated in the pathogenesis of various other disorders in addition to OS including cancer and neurodegenerative diseases. Influencing the activity of the MID1 protein complex is a promising new st…

2015

Purpose: The aim of this study was to investigate the interaction and co-localization of novel interacting proteins with the Leber congenital amaurosis (LCA) associated protein aryl hydrocarbon receptor interacting protein-like 1 (AIPL1). Methods: The CytoTrapXR yeast two-hybrid system was used to screen a bovine retinal cDNA library. A novel interaction between AIPL1 and members of the family of EB proteins was confirmed by directed yeast two-hybrid analysis and co-immunoprecipitation assays. The localization of AIPL1 and the EB proteins in cultured cells and in retinal cryosections was examined by immunofluorescence microscopy and cryo-immunogold electron microscopy. Results: Yeast two-hy…

Cells expressing markers of immature neurons in the amygdala of adult humans

2012

The polysialylated form of the neuronal cell adhesion molecule (PSA-NCAM) is expressed by immature neurons in the amygdala of adult mammals, including non-human primates. In a recent report we have also described the presence of PSA-NCAM-expressing cells in the amygdala of adult humans. Although many of these cells have been classified as mature interneurons, some of them lacked mature neuronal markers, suggesting the presence of immature neurons. We have studied, using immunohistochemistry, the existence and distribution of these immature neurons using post mortem material. We have also analysed the presence of proliferating cells and the association between immature neurons and specialise…

Long-term hydrocephalus alters the cytoarchitecture of the adult subventricular zone

2014

Hydrocephalus can develop secondarily to a disturbance in production, flow and/or absorption of cerebrospinal fluid. Experimental models of hydrocephalus, especially subacute and chronic hydrocephalus, are few and limited, and the effects of hydrocephalus on the subventricular zone are unclear. The aim of this study was to analyze the effects of long-term obstructive hydrocephalus on the subventricular zone, which is the neurogenic niche lining the lateral ventricles. We developed a new method to induce hydrocephalus by obstructing the aqueduct of Sylvius in the mouse brain, thus simulating aqueductal stenosis in humans. In 120-day-old rodents (n = 18 per group), the degree of ventricular d…

Integration of a radiation biomarker into modeling of thyroid carcinogenesis and post-Chernobyl risk assessment

2016

Strong evidence for the statistical association between radiation exposure and disease has been produced for thyroid cancer by epidemiological studies after the Chernobyl accident. However, limitations of the epidemiological approach in order to explore health risks especially at low doses of radiation appear obvious. Statistical fluctuations due to small case numbers dominate the uncertainty of risk estimates. Molecular radiation markers have been searched extensively to separate radiation-induced cancer cases from sporadic cases. The overexpression of the CLIP2 gene is the most promising of these markers. It was found in the majority of papillary thyroid cancers (PTCs) from young patients…

KIAA0556 is a novel ciliary basal body component mutated in Joubert syndrome

2015

Background Joubert syndrome (JBTS) and related disorders are defined by cerebellar malformation (molar tooth sign), together with neurological symptoms of variable expressivity. The ciliary basis of Joubert syndrome related disorders frequently extends the phenotype to tissues such as the eye, kidney, skeleton and craniofacial structures. Results Using autozygome and exome analyses, we identified a null mutation in KIAA0556 in a multiplex consanguineous family with hallmark features of mild Joubert syndrome. Patient-derived fibroblasts displayed reduced ciliogenesis potential and abnormally elongated cilia. Investigation of disease pathophysiology revealed that Kiaa0556-/- null mice possess…

Variations in genes regulating neuronal migration predict reduced prefrontal cognition in schizophrenia and bipolar subjects from mediterranean Spain…

2005

Both neural development and prefrontal cortex function are known to be abnormal in schizophrenia and bipolar disorder. In order to test the hypothesis that these features may be related with genes that regulate neuronal migration, we analyzed two genomic regions: the lissencephaly critical region (chromosome 17p) encompassing the LIS1 gene and which is involved in human lissencephaly; and the genes related to the platelet-activating-factor, functionally related to LIS1, in 52 schizophrenic patients, 36 bipolar I patients and 65 normal control subjects. In addition, all patients and the 25 control subjects completed a neuropsychological battery. Thirteen (14.8%) patients showed genetic varia…