1,721,124 research outputs found
Variably Protease-Sensitive Prionopathy: a Novel Disease of the Prion Protein
Full text linkVariably protease-sensitive prionopathy (VPSPr) is a novel disease involving the prion protein (PrP) that has clinical similarities with non-Alzheimer's dementias especially frontotemporal dementia, diffuse Lewis body disease, and normal pressure hydrocephalus. VPSPr can be distinguished from sporadic Creutzfeldt-Jakob disease (sCJD) especially for the characteristics of the abnormal PrP. Furthermore, although VPSPr like sCJD affects patients with the three PrP genotypes as determined by the common methionine/valine polymorphism, the allelic prevalence is very different in the two diseases. These findings suggest that VPSPr is basically different from classical prion diseases such as sCJD being perhaps more akin to other neurodegenerative dementia
Senile plaques in congophilic amyloid angiopathy show accumulation of amyloid precursor protein without cytoskeletal abnormalities
No full textGiant axonal neuropathy: acceleration of neurofilament transport in optic axons.
No full textGiant axonal neuropathies are a group of acquired and inherited human diseases morphologically characterized by accumulation of neurofilaments (NF) in enlargements of preterminal regions of central and peripheral axons. Slow axonal transport was studied in the optic systems of rats treated with 2,5-hexanedione, a toxic compound that produces an experimental model of giant axonal neuropathy. The transport rate of NF and of two other polypeptides of M(r) 64,000 and 62,000 were selectively increased. Other components of the slow axonal transport were not affected. Acceleration of labeled NF was also observed when 2,5-hexanedione was given after [35S]methionine administration. Morphometric analysis revealed that the number of NF and the axon size were decreased in regions of optic axons proximal to the enlargements. It is suggested that acceleration of NF transport leads to a longitudinal redistribution of NF: NF decrease proximally and increase distally, forming NF-containing enlargements. Evidence was obtained that polypeptides of M(r) 64,000 and 62,000 are cytoskeletal components related to intermediate filaments, normally migrating with the component a of the slow axonal transport. The 2,5-hexanedione axon may provide insight into the pathogenesis of inherited and acquired giant axonal neuropathies and offers a model to investigate the relationship between number of NF and axonal size in central axons
Coexistence of Both PrPSc Type 1 and 2 in sCJD: Does it Affect the Phenotype?
No full textIn sporadic Creutzfeldt-Jakob disease (sCJD) five phenotypically distinct subtypes
have been identified based on the methionine (M)/valine (V) polymorphic genotype of
codon 129 and two PK-resistant scrapie prion protein (PrPSc) types, which migrate in
gel to either 21 kDa (PrPSc type 1) or 19 kDa (PrPSc type 2). sCJD is characterized by
phenotypic heterogeneity. The co-existence of both PrPSc types has recently been
reported and may complicate the diagnosis.
In the present study we analyze the distribution of the two PrPSc types in various brain
areas as well as the PrPSc resistance to PK digestion using a rigorous procedure
according to Notari et al [Human PrPSc “Typing” pitfalls associated with the use of
type 1 selective antibodies combined with relative inefficient hydrolysis of PrPSc by
proteinase K, poster presentation, NeuroPrion 2006, Torino], with the intent of
assessing the co-occurrence of fully PK-resistant PrPSc types 1 and 2 in a ratio of
50:50 or 60:40 while ascertaining that intermediate fragments are completely digested.
We are studying the effect of the co-existence of the two PrPSc types, which occurs
in either the same or different brain regions, on the sCJD disease phenotype by
examining clinical history and neuropathological changes
Heidenhain Variant of Sporadic Creutzfeldt-Jakob Disease With the Co-Occurrence of Two Different Types of Prion Protein
No full textBovine spongiform encephalopathy. (chapter 1)
No full textBovine spongiform encephalopathy (BSE) is a fatal neurodegenerative disease of cattle caused by foodbome exposure to prions. First described in 1986, this novel disorder was clinically characterized by altered behavior, sensory changes, and locomotor signs. For almost two decades, BSE, now named classical BSE (C-type BSE), has been regarded as the only and exclusive prion disorder of cattle.
The introduction of an active surveillance system for BSE in 200l allowed the identification of two additional atypical forms of BSE, named H-type and L-type BSEs, because of distinct conformations of the pathological prion protein, or PrP‘°, with higher (H-type) or lower (L-type) electrophoietic mobility of the unglycosylated protease-resistant Prl”° fragment. To date, a total of 34 L-type BSE and 27 l-I-type BSE have been detected worldwide by routine BSE testing in older cattle. The clinical phenotypes of atypical BSE forms are still undefined in field animals, although information has been obtained from intraspecies transmission studies. Transmission studies to mice show that C-type, H-type, and L-type BSE forms display distinct molecular properties, consistent with the occurrence of three different prion strains. Intriguingly, upon serial passages, I-l-type and L-type BSEs may acquire C-type
properties, hence suggesting a possible role in the origin of BSE epidemics. Further, the evidence that atypical BSEs are transmissible to mammals, including nonhuman primates, are issues that raise public health concerns
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