Sustained Depolarization Induces Gene Expression Pattern Changes Related to Synaptic Plasticity in a Human Cholinergic Cellular Model.

Neuronal gene expression in the brain dynamically responds to synaptic activity. The interplay among synaptic activity, gene expression, and synaptic plasticity has crucial implications for understanding the pathophysiology of diseases such as Alzheimer's disease and epilepsy. These diseases are marked by synaptic dysfunction that affects the expression patterns of neuroprotective genes that are incompletely understood.

CD33 rs2455069 SNP: Correlation with Alzheimer's Disease and Hypothesis of Functional Role.

The CD33 gene encodes for a member of the sialic-acid-binding immunoglobulin-type lectin (Siglec) family, and is one of the top-ranked Alzheimer’s disease (AD) risk genes identified by genome-wide association studies (GWAS). Many CD33 polymorphisms are associated with an increased risk of AD, but the function and potential mechanism of many CD33 single-nucleotide polymorphisms (SNPs) in promoting AD have yet to be elucidated. We recently identified the CD33 SNP rs2455069-A>G (R69G) in a familial form of dementia.

LINC00473 as an Immediate Early Gene under the Control of the EGR1 Transcription Factor.

Immediate early genes play an essential role in cellular responses to different stimuli. Many of them are transcription factors that regulate the secondary response gene expression. Non-coding RNAs may also be involved in this regulatory cascade.

CD33 and SIGLECL1 Immunoglobulin Superfamily Involved in Dementia.

Sialic acid-binding immunoglobulin-type lectins, which are predominantly expressed in immune cells, represent a family of immunomodulatory receptors with inhibitory and activating signals, in both healthy and disease states. Genetic factors are important in all forms of dementia, especially in early onset dementia. CD33 was recently recognized as a genetic risk factor for Alzheimer disease (AD).

Clinical and Molecular Characterization of a Novel Progranulin Deletion Associated with Different Phenotypes.

Background: Mutations in the GRN gene are causative for an autosomal dominant form of frontotemporal dementia.

Objective/methods: The objective of the present study is to describe clinical and molecular features of three siblings harboring the GRN deletion NM_002087.3:c.

Identification, Characterization, and Regulatory Mechanisms of a Novel EGR1 Splicing Isoform.

EGR1 is a transcription factor expressed in many cell types that regulates genes involved in different biological processes including growth, proliferation, and apoptosis. Dysregulation of EGR1 expression has been associated with many pathological conditions such as tumors and brain diseases. Known molecular mechanisms underlying the control of EGR1 function include regulation of transcription, mRNA and protein stability, and post-translational modifications.

Circulating levels of IL-1 family cytokines and receptors in Alzheimer's disease: new markers of disease progression?

Background: Although the mechanisms underlying AD neurodegeneration are not fully understood, it is now recognised that inflammation could play a crucial role in the initiation and progression of AD neurodegeneration. A neuro-inflammatory network, based on the anomalous activation of microglial cells, includes the production of a number of inflammatory cytokines both locally and systemically. These may serve as diagnostic markers or therapeutic targets for AD neurodegeneration.

GRN deletion in familial frontotemporal dementia showing association with clinical variability in 3 familial cases.

Progranulin (GRN) gene mutations have been genetically associated with frontotemporal dementia (FTD) and are present in about 23% of patients with familial FTD. However, the neurobiology of this secreted glycoprotein remains unclear. Here, we report the identification of 3 pedigrees of Southern Italian extraction in whom FTD segregates with autosomal dominant inheritance patterns.

Imidazole-stabilized gold nanoparticles induce neuronal apoptosis: an in vitro and in vivo study.

Gold nanoparticles are increasingly being employed in innovative biological applications thanks to their advantages of material- and size-dependent physics and chemical interactions with the cellular systems. On the other hand, growing concern has emerged on the toxicity which would render gold-based nanoparticles harmful to cell cultures, animals, and humans. Emerging attention is focused on the interaction of gold nanoparticles with nervous system, especially regarding the ability to overcome the blood-brain barrier (BBB) which represents the major impediment to the delivery of therapeutics into the brain.

Donor splice-site mutation in CUL4B is likely cause of X-linked intellectual disability.

X-linked intellectual disability is the most common form of cognitive disability in males. Syndromic intellectual disability encompasses cognitive deficits with other medical and behavioral manifestations. Recently, a large family with a novel form of syndromic X-linked intellectual disability was characterized.

Cortical metabolic deficits in a rat model of cholinergic basal forebrain degeneration.

Evidence indicates that the degeneration of basal forebrain cholinergic neurons may represent an important factor underlying the progressive cognitive decline characterizing Alzheimer's disease (AD). However, the nature of the relationship between cholinergic depletion and AD is not fully elucidated. This study aimed at clarifying some aspects of the relation existing between deficits in cerebral energy metabolism and degeneration of cholinergic system in AD, by investigating the neuronal metabolic activity of several cortical areas after depletion of basal forebrain cholinergic neurons.

Structural chromosomal variations in neurological diseases.

Background: Significant advancement in the identification of genetic mutations and molecular pathways underlying Mendelian neurologic disorders was accomplished by using the methods of linkage, gene cloning, sequencing, mutation, and functional analyses, in the 1990s. Subsequently, the Human Genome Project defined the entire sequence of the genome providing reference for any pathologic condition, and identified single nucleotide polymorphisms as a means for whole genome association studies and linkage disequilibrium mapping in common, complex trait diseases. Simultaneously, data also emerged describing the structural chromosomal variations, and it became increasingly recognized that in addition to the more traditional mutation types, gene copy number variations (CNVs) contribute to normal variability in human phenotypes and may underlie the development of diseases with Mendelian inheritance, complex trait, or sporadic presentation.

Variants of ST8SIA1 are associated with risk of developing multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system of unknown etiology with both genetic and environmental factors playing a role in susceptibility. To date, the HLA DR15/DQ6 haplotype within the major histocompatibility complex on chromosome 6p, is the strongest genetic risk factor associated with MS susceptibility. Additional alleles of IL7 and IL2 have been identified as risk factors for MS with small effect.

Highly variable penetrance in subjects affected with cavernous cerebral angiomas (CCM) carrying novel CCM1 and CCM2 mutations.

Cavernous vascular malformations may affect brain and out-of-brain tissues. In most cases, cerebral cavernous malformations (CCMs) involve the brain alone, and are rarely associated with skin hemangiomas, spinal cord, retinal, hepatic or vertebral lesions. CCMs can cause seizures, intracranial and spinal haemorrhages, focal neurological deficits, and migraine-like headaches.

Arvanil and anandamide up-regulate CD36 expression in human peripheral blood mononuclear cells.

In this study we analysed the regulation of gene expression by arvanil and anandamide in human peripheral blood mononuclear cells (PBMCs) to clarify their immunosuppressive properties. PBMCs were activated, leading to CD36 down regulation, that was normalized by arvanil and anandamide. We used microarray technology to identify a regulatory pattern associated with cell proliferation in the presence of both substances.

A novel frameshift mutation of FOXC2 gene in a family with hereditary lymphedema-distichiasis syndrome associated with renal disease and diabetes mellitus.

Lymphedema-distichiasis (LD) syndrome is a clinically variable autosomal dominant disorder. The disorder is caused by mutations in the forkhead transcription factor FOXC2 gene on chromosome band 16q24.3.

Second family with hearing impairment linked to 19q13 and refined DFNA4 localisation.

Until now, over 30 loci have been identified by linkage analysis of affected families that segregate non-syndromic and dominantly inherited forms of hearing impairment (DFNA). A German family with a non-syndromic progressive hearing impairment transmitted in autosomal dominant mode was linked to 19q13.3-q13.

Linkage analysis conditional on HLA status in a large North American pedigree supports the presence of a multiple sclerosis susceptibility locus on chromosome 12p12.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with a probable immune-mediated pathogenesis. Strong evidence supports the hypothesis that MS is determined by genetic and environmental factors, but these factors remain largely undefined. The genetic component is suggested by a higher concordance rate in monozygotic (28%) versus dizygotic (5%) twins as well as familial recurrence risk.