Serum MicroRNAs as Predictors of Diagnosis and Drug-resistance in Temporal Lobe Epilepsy: A Preliminary Study.

Objective: Temporal lobe epilepsy (TLE) is the most common form of refractory focal epilepsy, and the current clinical diagnosis is based on EEG, clinical neurological history and neuroimaging findings.

Methods: So far, there are no blood-based molecular biomarkers of TLE to support clinical diagnosis, despite the pathogenic mechanisms underlying TLE involving defects in the regulation of gene expression. MicroRNAs (miRNAs) have emerged as important post-transcriptional regulators of gene expression.

A Comprehensive Examination of the Role of Epigenetic Factors in Multiple Sclerosis.

According to various research, the risk of multiple sclerosis (MS) is strongly influenced by genetic variations. Population, familial, and molecular studies provide strong empirical support for a polygenic pattern of inheritance, mainly due to relatively common allelic variants in the general population. The strongest MS susceptibility locus, which was unmistakably identified in tested populations, is the major histocompatibility complex on chromosome 6p21.

Extracellular Vesicles in Multiple Sclerosis: Their Significance in the Development and Possible Applications as Therapeutic Agents and Biomarkers.

Extracellular vesicles (EVs) are "micro-shuttles" that play a role as mediators of intercellular communication. Cells release EVs into the extracellular environment in both physiological and pathological conditions and are involved in intercellular communication, due to their ability to transfer proteins, lipids, and nucleic acids, and in the modulation of the immune system and neuroinflammation. Because EVs can penetrate the blood-brain barrier and move from the central nervous system to the peripheral circulation, and vice versa, recent studies have shown a substantial role for EVs in several neurological diseases, including multiple sclerosis (MS).

Circulating miRNAs in progressive supranuclear palsy: Recent evidence and future challenges.

Numerous studies have highlighted the importance of microRNA (miRNAs) in neurodegenerative diseases. However, the miRNA profiles in progressive supranuclear palsy (PSP) patients have been rarely reported. Recent evidence suggested a possible role of some dysregulated miRNAs in the cerebrospinal fluid (CSF) of PSP patients in the pathogenesis of the disease.

Non-Coding RNAs: New Biomarkers and Therapeutic Targets for Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy; it is considered a network disorder associated with structural changes. Incomplete knowledge of the pathological changes in TLE complicates a therapeutic approach; indeed, 30 to 50% of patients with TLE are refractory to drug treatment. Non-coding RNAs (ncRNAs), acting as epigenetic factors, participate in the regulation of the pathophysiological processes of epilepsy and are dysregulated during epileptogenesis.

Hyper-religiosity and visual hallucinations in a patient with frontotemporal dementia carrying a double variant in GRN gene.

: Hyper-religiosity has been reported in patients affected by frontotemporal dementia (FTD) with asymmetrical, predominantly right-sided frontotemporal atrophy. : We report a FTD patient carrying a double genetic variant (p.Cys139Arg and c.

Roles of Non-Coding RNAs as Novel Diagnostic Biomarkers in Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting 5%of the elderly population. Currently, the diagnosis of PD is mainly based on clinical features and no definitive diagnostic biomarkers have been identified. The discovery of biomarkers at the earliest stages of PD is of extreme interest.

Circulating microRNA: The Potential Novel Diagnostic Biomarkers to Predict Drug Resistance in Temporal Lobe Epilepsy, a Pilot Study.

MicroRNAs (miRNAs) are small noncoding RNAs that have emerged as new potential epigenetic biomarkers. Here, we evaluate the efficacy of six circulating miRNA previously described in the literature as biomarkers for the diagnosis of temporal lobe epilepsy (TLE) and/or as predictive biomarkers to antiepileptic drug response. We measured the differences in serum miRNA levels by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays in a cohort of 27 patients (14 women and 13 men; mean ± SD age: 43.

Exosomal miRNAs as Potential Diagnostic Biomarkers in Alzheimer's Disease.

Alzheimer's disease (AD), a neurodegenerative disease, is linked to a variety of internal and external factors present from the early stages of the disease. There are several risk factors related to the pathogenesis of AD, among these exosomes and microRNAs (miRNAs) are of particular importance. Exosomes are nanocarriers released from many different cell types, including neuronal cells.

Potential Role of miRNAs as Theranostic Biomarkers of Epilepsy.

Epilepsy includes a group of disorders of the brain characterized by an enduring predisposition to generate epileptic seizures. Although familial epilepsy has a genetic component and heritability, the etiology of the majority of non-familial epilepsies has no known associated genetic mutations. In epilepsy, recent epigenetic profiles have highlighted a possible role of microRNAs in its pathophysiology.

Exosome-associated miRNA profile as a prognostic tool for therapy response monitoring in multiple sclerosis patients.

Multiple sclerosis (MS) is an autoimmune pathology leading to neurodegeneration. Because of the complexity and heterogenic etiology of this disease, diagnosis and treatment for individual patients are challenging. Exosome-associated microRNAs (miRNAs) have recently emerged as a new class of diagnostic biomarkers involved in both autoimmune and neurologic disorders.

An SNP site in pri-miR-124, a brain expressed miRNA gene, no contribution to mesial temporal lobe epilepsy in an Italian sample.

Mesial temporal lobe epilepsy (MTLE) is the most common type of refractory epilepsy and is usually associated with hippocampal sclerosis (Hs). The pathogenesis of MTLE involves many biological pathways, some of which seem to be regulated by microRNAs (miRNAs). Increasing evidence shows that single nucleotide polymorphisms (SNPs) or mutations in miRNAs sequence may affect the processing and function of miRNAs and participate in the occurrence of diseases.

DEPDC5 mutations are not a frequent cause of familial temporal lobe epilepsy.

Mutations in the DEPDC5 (DEP domain-containing protein 5) gene are a major cause of familial focal epilepsy with variable foci (FFEVF) and are predicted to account for 12-37% of families with inherited focal epilepsies. To assess the clinical impact of DEPDC5 mutations in familial temporal lobe epilepsy, we screened a collection of Italian families with either autosomal dominant lateral temporal epilepsy (ADLTE) or familial mesial temporal lobe epilepsy (FMTLE). The probands of 28 families classified as ADLTE and 17 families as FMTLE were screened for DEPDC5 mutations by whole exome or targeted massive parallel sequencing.

Polymorphism of the multidrug resistance 1 gene MDR1/ABCB1 C3435T and response to antiepileptic drug treatment in temporal lobe epilepsy.

Purpose: A synonymous C to T variant at position 3435 (c.3435C>T) is one common polymorphism of the multidrug resistant 1 (MDR1) gene, which encodes the major transmembrane efflux transporter P-glycoprotein. It has been suggested that this polymorphism, and more specifically the 3435CC genotype, may be associated with the response to antiepileptic drug treatment.

Autosomal dominant lateral temporal epilepsy (ADLTE): absence of chromosomal rearrangements in LGI1 gene.

Mutations of leucine-rich, glioma inactivated 1 (LGI1) gene are found in about half of the families with autosomal dominant lateral temporal epilepsy (ADLTE). More recently a LGI1 heterozygous microdeletion was found in a single ADLTE family, suggesting that submicroscopic chromosomal abnormalities should be investigated in cases negative for LGI1 mutations. This study examines whether microdeletions and duplications of the LG1 gene occurred in eight ADLTE families and 20 sporadic patients that were negative for LGI1 mutations.

No evidence for a role of the coding variant of the Toll-like receptor 4 gene in temporal lobe epilepsy.

Purpose: There is evidence that inflammatory mechanisms play a role in the pathogenesis of temporal lobe epilepsy (TLE). Coding variants in Toll-like receptor 4 (TLR4) gene have been reported to be associated with inflammatory diseases. The aim of this study was to determine whether a functional polymorphism rs4986790 in the TLR4 gene is associated with susceptibility and clinical features of TLE.

Failure to confirm association of a polymorphism in KCNMB4 gene with mesial temporal lobe epilepsy.

A recent study has implicated a tagging single nucleotide polymorphism (SNP) rs398702 located 3' of KCNMB4 (encoding calcium-activated potassium channel, subfamily M subunit beta 4) as a possible susceptibility allele for mesial temporal lobe epilepsy (mTLE). Such a finding warrants a further well-powered study in additional carefully phenotyped cohorts. Here we examined the role of the SNP (rs398702) in a cohort of 332 patients (182 women and 150 men; mean±SD age: 47.

The BDNF Val66Met polymorphism has opposite effects on memory circuits of multiple sclerosis patients and controls.

Episodic memory deficits are frequent symptoms in Multiple Sclerosis and have been associated with dysfunctions of the hippocampus, a key region for learning. However, it is unclear whether genetic factors that influence neural plasticity modulate episodic memory in MS. We thus studied how the Brain Derived Neurotrophic Factor Val(66)Met genotype, a common polymorphism influencing the hippocampal function in healthy controls, impacted on brain networks underlying episodic memory in patients with Multiple Sclerosis.

Relationship between genetic variant in pre-microRNA-146a and genetic predisposition to temporal lobe epilepsy: a case-control study.

There is evidence that inflammatory mechanisms play a role in the pathogenesis of temporal lobe epilepsy (TLE). MicroRNAs (miRNAs), a class of small non-coding endogenous RNAs, which negatively regulate target gene expression, have shown different expression patterns in immune diseases. Recently, several miRNAs have been found to be differentially expressed in animal models of TLE.

A functional genetic variation of the 5-HTR2A receptor affects age at onset in patients with temporal lobe epilepsy.

The 1354C>T polymorphism of the 5-hydroxytryptamine receptor 2A gene (5-HTR2A) was implicated in human memory performance. We investigated the relationship between this polymorphism and cognitive function in patients with temporal lobe epilepsy (TLE). We also evaluated if this polymorphism could influence the phenotype.

Contribution of cerebrospinal fluid thymosin β4 levels to the clinical differentiation of Creutzfeldt-Jakob disease.

Objective: To asses thymosin β4 specificity as relevant to the diagnosis of Creutzfeldt-Jakob disease (CJD).

Design: A matrix-assisted laser desorption ionization time-of-flight mass spectrometry protein profiling analysis was applied to several neurological disorders that are known to lead to dementia. The relative peak area (percentage of area) of the thymosin β4 MS signal was taken into account.

A functional polymorphism in the SCN1A gene does not influence antiepileptic drug responsiveness in Italian patients with focal epilepsy.

A splice site variation (c.603-91G>A or rs3812718) in the SCN1A gene has been claimed to influence efficacy and dose requirements of carbamazepine and phenytoin. We investigated the relationship between c.