Search results for "Prion Diseases"
showing 10 items of 11 documents
The cognitive profile of prion disease: a prospective clinical and imaging study
2015
Objectives Prion diseases are dementing illnesses with poorly defined neuropsychological features. This is probably because the most common form, sporadic Creutzfeldt-Jakob disease, is often rapidly progressive with pervasive cognitive decline making detailed neuropsychological investigation difficult. This study, which includes patients with inherited, acquired (iatrogenic and variant) and sporadic forms of the disease, is the only large-scale neuropsychological investigation of this patient group ever undertaken and aimed to define a neuropsychological profile of human prion diseases. Methods A tailored short cognitive examination of all of the patients (n = 81), with detailed neuropsycho…
Novel approaches in diagnosis and therapy of Creutzfeldt-Jakob disease.
2000
The scrapie prion protein, PrP(Sc), as well as its peptide fragment, PrP106-126, are toxic on neuronal cells, resulting in cell death by an apoptotic, rather than necrotic mechanism. The apoptotic process of neuronal cells induced by prion protein supports diagnosis and offers potential targets for therapeutic intervention of the prion diseases. Among the cerebrospinal fluid (CSF) proteins, which may serve as markers of neuronal cell death associated with prion diseases, the 14-3-3 protein(s) turned out to be the most promising one. A new sensitive assay allows the detection of even small changes in the normally low levels of these proteins. In vitro, the toxic effects displayed by PrP(Sc) …
Neuroprotective effect of flupirtine in prion disease
2003
Apoptotic neuronal cell death is a hallmark of prion diseases. The apoptotic process in neuronal cells is thought to be caused by the scrapie prion protein, PrPSc, and can be experimentally induced by its peptide fragment, PrP106-126. This process is a target for potential drugs to combat prion disease or to ameliorate its symptoms. Flupirtine (Katadolon), a pyridine derivative that is in clinical use as a nonopioid analgesic, has a potent cytoprotective effect, at concentrations above 1 microg/mL, on neuronal cells treated with PrP(Sc) or PrP106-126. This drug acts as an N-methyl-D-aspartate (NMDA) antagonist, but does not bind to NMDA receptors. Flupirtine normalizes the level of intracel…
Glycosylation deficiency at either one of the two glycan attachment sites of cellular prion protein preserves susceptibility to bovine spongiform enc…
2004
The conversion into abnormally folded prion protein (PrP) plays a key role in prion diseases. PrP(C) carries two N-linked glycan chains at amino acid residues 180 and 196 (mouse). Previous in vitro data indicated that the conversion process may not require glycosylation of PrP. However, it is conceivable that these glycans function as intermolecular binding sites during the de novo infection of cells on susceptible organisms and/or play a role for the interaction of both PrP isoforms. Such receptor-like properties could contribute to the formation of specific prion strains. However, in earlier studies, mutations at the glycosylation sites of PrP led to intracellular trafficking abnormalitie…
Distinct neuropsychological profiles correspond to distribution of cortical thinning in inherited prion disease caused by insertional mutation
2012
Background The human prion diseases are a group of universally fatal neurodegenerative disorders associated with the auto-catalytic misfolding of the normal cell surface prion protein (PrP). Mutations causative of inherited human prion disease (IPD) include an insertion of six additional octapeptide repeats (6-OPRI) and a missense mutation (P102L) with large families segregating for each mutation residing in southern England. Here we report for the first time the neuropsychological and clinical assessments in these two groups. Method The cognitive profiles addressing all major domains were obtained for 26 patients (18 6-OPRI, 8 P102L) and the cortical thickness determined using 1.5T MRI in …
Mathematical models for the diffusion magnetic resonance signal abnormality in patients with prion diseases
2014
In clinical practice signal hyperintensity in the cortex and/or in the striatum on magnetic resonance (MR) diffusion-weighted images (DWIs) is a marker of sporadic Creutzfeldt–Jakob Disease (sCJD). MR diagnostic accuracy is greater than 90%, but the biophysical mechanisms underpinning the signal abnormality are unknown. The aim of this prospective study is to combine an advanced DWI protocol with new mathematical models of the microstructural changes occurring in prion disease patients to investigate the cause of MR signal alterations. This underpins the later development of more sensitive and specific image-based biomarkers. DWI data with a wide a range of echo times and diffusion weightin…
Pharmacological intervention in age-associated brain disorders by Flupirtine: Alzheimer’s and Prion diseases
1998
Alzheimer's disease, a major form of dementia in the elderly has become an increasingly important health problem in developed countries. In vitro studies on primary neurons demonstrate that Flupirtine (Katadolon) at a concentration of 1 microg/ml, significantly reduces the neurotoxic (apoptotic) effect displayed by A beta25-35, a segment of the amyloid beta-protein precursor the etiologic agent of Alzheimer's disease. Flupirtine, which has been in clinical use since 10 years ago, prevents the toxic effect of PrP, the presumed etiologic agent of the Creutzfeldt-Jakob disease as well as the excitatory amino acid glutamate on cortical neurons. Flupirtine displays a bimodal activity. Its strong…
Temporal dynamics of hippocampal neurogenesis in chronic neurodegeneration.
2014
Increased neurogenesis has been reported in neurodegenerative disease, but its significance is unclear. In a mouse model of prion disease, Gomez-Nicola et al. detect increased neurogenesis in the dentate gyrus that partially counteracts neuronal loss. Targeting neurogenesis may have therapeutic potential.
The neuropsychology of variant CJD: a comparative study with inherited and sporadic forms of prion disease.
2005
Objective: To assess cognitive function in variant Creutzfeldt-Jakob disease (vCJD). We describe the neuropsychological profiles of 10 cases and compare these data with cross sectional data obtained from patients with histologically confirmed sporadic CJD and cases with inherited prion disease with confirmed mutations in the prion protein gene. Methods: Patients referred to the Specialist Cognitive Disorders Clinic at the National Hospital for Neurology and Neurosurgery and the National Prion Clinic at St Mary's Hospital, London for further investigation of suspected CJD were recruited into the study. The neuropsychological test battery evaluated general intelligence, visual and verbal memo…
Prions, mad cow disease, and preventive measures: a critical appraisal
2003
In 1996 the first key epidemiological study on bovine spongiform encephalitis (BSE) appeared in the renowned journal Nature [1]. In that article it was estimated that by the year 1996, some 750,000 cows with BSE had entered the food chain in Great Britain. Accordingly, millions of people in GB must have consumed contaminated meat. That same year the first report on a new form of Creutzfeldt-Jakob disease [variant (v) CJD] manifesting in young patients appeared [26]. A connection between this disease and BSE was assumed. In view of the suspicion that the use of meat and bone meal (MBM) had led to the outbreak of BSE, feeding with MBM was banned in the year 1988. The number of new BSE infecti…