Perry Disease: Expanding the Genetic Basis.

Background: Perry disease (or Perry syndrome [PS]) is a hereditary neurodegenerative disorder inevitably leading to death within few years from onset. All previous cases with pathological confirmation were caused by mutations within the cytoskeleton-associated protein glycine-rich (CAP-Gly) domain of the gene.

Objectives: This paper presents the first clinicopathological report of PS due to a novel mutation outside the CAP-Gly domain.

The Underlying Pathogenesis of Neurovascular Compression Syndromes: A Systematic Review.

Neurovascular compression syndromes (NVC) are challenging disorders resulting from the compression of cranial nerves at the root entry/exit zone. Clinically, we can distinguish the following NVC conditions: trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia. Also, rare cases of geniculate neuralgia and superior laryngeal neuralgia are reported.

Diagnostic accuracy of cerebrospinal fluid biomarkers in genetic prion diseases.

Genetic prion diseases are a rare and diverse group of fatal neurodegenerative disorders caused by pathogenic sequence variations in the prion protein gene, PRNP. Data on CSF biomarkers in patients with genetic prion diseases are limited and conflicting results have been reported for unclear reasons. Here, we aimed to analyse the diagnostic accuracy of CSF biomarkers currently used in prion clinical diagnosis in 302 symptomatic genetic prion disease cases from 11 prion diagnostic centres, encompassing a total of 36 different pathogenic sequence variations within the open reading frame of PRNP.

mRNA and miRNA Expression Analyses of the //miR-17-92 Network in the Most Common Pediatric Brain Tumors.

Numerous molecular factors disrupt the correctness of the cell cycle process leading to the development of cancer due to increased cell proliferation. Among known causative factors of such process is abnormal gene expression. Nowadays in the light of current knowledge such alterations are frequently considered in the context of mRNA-miRNA correlation.

If Artificial In Vitro Microenvironment Can Influence Tumor Drug Resistance Network via Modulation of lncRNA Expression?-Comparative Analysis of Glioblastoma-Derived Cell Culture Models and Initial Tumors In Vivo.

The tumor resistance of glioblastoma cells in vivo is thought to be enhanced by their heterogeneity and plasticity, which are extremely difficult to curb in vitro. The external microenvironment shapes the molecular profile of tumor culture models, thus influencing potential therapy response. Our study examines the expression profile of selected lncRNAs involved in tumor resistance network in three different glioblastoma-derived models commonly utilized for testing drug response in vitro.

Identification of novel risk loci and causal insights for sporadic Creutzfeldt-Jakob disease: a genome-wide association study.

Background: Human prion diseases are rare and usually rapidly fatal neurodegenerative disorders, the most common being sporadic Creutzfeldt-Jakob disease (sCJD). Variants in the PRNP gene that encodes prion protein are strong risk factors for sCJD but, although the condition has similar heritability to other neurodegenerative disorders, no other genetic risk loci have been confirmed. We aimed to discover new genetic risk factors for sCJD, and their causal mechanisms.

microRNA interaction with MAPK and AKT pathways in paediatric brain tumours - preliminary results and review of the literature.

Nowadays molecular investigations have a significant impact on the understanding of primary brain tumour biology,as well as on their classification and progress in the treatment modalities. Among novel type of biomarkers with potential therapeutic value, microRNAs (miRNAs) are considered in some cases. miRNAs are small molecules regu-lating gene expression, including genes encoding key proteins involved in signalling pathways responsible for growth and cell survival during tumour formation.

Artificial microenvironment of in vitro glioblastoma cell cultures changes profile of miRNAs related to tumor drug resistance.

The in vitro environment can influence not only the molecular background of glioblastoma drug-resistance and treatment efficiency, but also the mechanisms and pathways of cell death. Both crucial molecular pathways and the deregulation of miRNAs are thought to participate in tumor therapy-resistance. The aim of our study is to examine the potential influence of ex vivo conditions on the expression of miRNAs engaged in the machinery of tumor-drug resistance, since in vitro models are commonly used for testing new therapeutics.

Sensitive detection of FGFR1 N546K mosaic mutation in patient with encephalocraniocutaneous lipomatosis and pilocytic astrocytoma.

Encephalocraniocutaneous lipomatosis (ECCL) is a rare neurocutaneous disorder, with only about 100 cases reported worldwide. It is characterized by congenital lesions of the eye, skin, and central nervous system. Only recently, potential causative FGFR1 point mutations have been identified in brain tumors and cultured skin biopsies from patients with this condition.

Expression-based decision tree model reveals distinct microRNA expression pattern in pediatric neuronal and mixed neuronal-glial tumors.

Background: The understanding of the molecular biology of pediatric neuronal and mixed neuronal-glial brain tumors is still insufficient due to low frequency and heterogeneity of those lesions which comprise several subtypes presenting neuronal and/or neuronal-glial differentiation. Important is that the most frequent ganglioglioma (GG) and dysembryoplastic neuroepithelial tumor (DNET) showed limited number of detectable molecular alterations. In such cases analyses of additional genomic mechanisms seem to be the most promising.

Axonal changes in experimental prion diseases recapitulate those following constriction of postganglionic branches of the superior cervical ganglion: a comparison 40 years later.

The major neurological feature of prion diseases is a neuronal loss accomplished through either apoptosis or autophagy. In this review, I compared axonal alterations in prion diseases to those described 40 years earlier as a result of nerve ligation. I also demonstrated that autophagic vacuoles and autophagosomes are a major part of dystrophic neurites.

Kuru, the First Human Prion Disease.

Kuru, the first human prion disease was transmitted to chimpanzees by D. Carleton Gajdusek (1923⁻2008). In this review, we summarize the history of this seminal discovery, its anthropological background, epidemiology, clinical picture, neuropathology, and molecular genetics.

Light and electron microscopic studies of the 139A-H strain of scrapie passaged in hamsters.

We report here the light and electron microscopic neuropathology of the 139A-H strain of scrapie passaged in Syrian golden hamsters. The general neuropathological picture consisted of the spongiform change and severe astrocytic gliosis. The topography of prion protein (PrP) was variable, the highest signal was observed in the CA2-molecular layer, CA1-pyramidal and entorhinal cortex.

Dystrophic neurites accumulating autophagic vacuoles show early stages of neuritic destruction.

We re-examined the database of some 20,000 electron micrographs from the Echigo-1, the 263K-strain or the 22C-H of scrapie-infected hamsters to look for the cytoplasmic clearance. We reevaluated the largest database in the world of photographed dystrophic neurites for the presence of cytoplasmic clearance as shown in transgenic fruit flies transfected with A-42. In several neurites, we found electron-lucent areas not bound by any membranes or only partially bound; thus, they were not autophagic vacuoles as the latter are membrane-bound and contain cargo.

Cerebrospinal fluid neurofilament light in suspected sporadic Creutzfeldt-Jakob disease.

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of human prion disease. It is invariably fatal and displays a short clinical disease stage. The key event in sCJD is the propagation of a beta-sheet rich conformer of the physiological PrP protein, known as PrP.

Morphometric analysis of mitochondria in lymphocytes of patients with exacerbations of chronic obstructive pulmonary disease - pilot study.

Introduction: Exacerbations of chronic obstructive pulmonary disease (ECOPD) are important events in the course of the disease, negatively influencing health status and disease progression. Therefore, there is a strong need for deeper understanding of the pathology of ECOPD to elaborate new therapeutic approaches and ameliorate prognoses. Contributions of mitochondria to pathobiology of COPD are still under investigation, although growing evidence suggests their important role in this disease.

Regulatory region single nucleotide polymorphisms of the apolipoprotein E gene as risk factors for Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by a complex aetiology. The ε4 allel of the apolipoprotein E gene (APOE) is the only confirmed genetic risk factor for the development of AD. In addition, polymorphisms at the promoter region of the APOE gene are assumed to modulate the susceptibility to AD by their different affinity to the transcription factors thus affecting the expression of the gene.

Cerebrospinal fluid neurofilament light levels in neurodegenerative dementia: Evaluation of diagnostic accuracy in the differential diagnosis of prion diseases.

Introduction: Neurofilament light (NFL) levels in the cerebrospinal fluid are increased in several neurodegenerative dementias. However, their diagnostic accuracy in the differential diagnostic context is unknown.

Methods: Cerebrospinal fluid NFL levels were quantified in nonprimarily neurodegenerative neurological and psychiatric diseases (n = 122), mild cognitive impairment (n = 48), Alzheimer's disease (n = 108), dementia with Lewy bodies/Parkinson's disease dementia (n = 53), vascular dementia (n = 46), frontotemporal dementia (n = 41), sporadic Creutzfeldt-Jakob disease (sCJD, n = 132), and genetic prion diseases (n = 182).

Robust autophagy in optic nerves of experimental Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker disease.

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Electron microscopic and confocal laser microscopy analysis of amyloid plaques in chronic wasting disease transmitted to transgenic mice.

We report here on the ultrastructure of amyloid plaques in chronic wasting disease (CWD) transmitted to Tg20 transgenic mice overexpressing prion protein (PrP). We identified three main types of amyloid deposits in mCWD: large amyloid deposits, unicentric plaques similar to kuru plaques in human prion diseases and multicentric plaques reminiscent of plaques typical of GSS. The most unique type of plaques were large subpial amyloid deposits.

Urinary F-Isoprostane Concentration as a Poor Prognostic Factor After Subarachnoid Hemorrhage.

Background: The role of isoprostanes in cerebral vasospasm (CVS) following aneurysmal subarachnoid hemorrhage (aSAH) is controversial. Recent studies have suggested that the level of isoprostanes in cerebrospinal fluid could play a role in outcomes of patients with aSAH. We measured concentration of urinary F-isoprostanes (F-IsoPs), which is simple and noninvasive.

Glioblastoma-derived cells unveil the spectrum of drug resistance capability - comparative study of tumour chemosensitivity in different culture systems.

Resistance to cancer drugs is a complex phenomenon which could be influenced by conditions. However, tumour-derived cell cultures are routinely used for studies related to mechanisms of drug responsiveness or the search for new therapeutic approaches. The purpose of our work was to identify the potential differences in drug resistance and response to treatment of glioblastoma with the use of three models: traditional adherent culture, serum-free spheroid culture and novel adherent serum-free culture.

Altered Ca homeostasis induces Calpain-Cathepsin axis activation in sporadic Creutzfeldt-Jakob disease.

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent form of human prion disease and it is characterized by the presence of neuronal loss, spongiform degeneration, chronic inflammation and the accumulation of misfolded and pathogenic prion protein (PrP). The molecular mechanisms underlying these alterations are largely unknown, but the presence of intracellular neuronal calcium (Ca) overload, a general feature in models of prion diseases, is suggested to play a key role in prion pathogenesis.Here we describe the presence of massive regulation of Ca responsive genes in sCJD brain tissue, accompanied by two Ca-dependent processes: endoplasmic reticulum stress and the activation of the cysteine proteases Calpains 1/2.