In Creutzfeldt-Jakob disease (CJD), molecular typing based on the size of the protease resistant core of the disease-associated prion protein (PrP(Sc) ) and the M/V polymorphism at codon 129 of the PRNP gene correlates with the clinico-pathologic subtypes. Approximately 95% of the sporadic 129MM CJD patients are characterized by cerebral deposition of type 1 PrP(Sc) and correspond to the classic clinical CJD phenotype. The rare 129MM CJD patients with type 2 PrP(Sc) are further subdivided in a cortical and a thalamic form also indicated as sporadic fatal insomnia. We observed two young patients with MM2-thalamic CJD. Main neuropathological features were diffuse, synaptic PrP immunoreactivity in the cerebral cortex and severe neuronal loss and gliosis in the thalamus and olivary nucleus. Western blot analysis showed the presence of type 2A PrP(Sc) . Challenge of transgenic mice expressing 129MM human PrP showed that MM2-thalamic sporadic CJD (sCJD) was able to transmit the disease, at variance with MM2-cortical sCJD. The affected mice showed deposition of type 2A PrP(Sc) , a scenario that is unprecedented in this mouse line. These data indicate that MM2-thalamic sCJD is caused by a prion strain distinct from the other sCJD subtypes including the MM2-cortical form.
Our study suggests that in the acute phase of the cerebral infarction CRP might be either a marker of cardioembolism or a predictive factor for short-term mortality.
Alzheimer disease (AD) is the most prevalent neurodegenerative disease, characterized by an increased deposition of β-amyloid (Abeta) within the central nervous system, leading to neuronal death. The availability of effective models, in which confirming novel pathogenic hypotheses and developing therapeutic targets, represents a very important goal for the field of AD. Fibroblasts from these patients may be relevant models in which addressing these issues, as they display biochemical alterations mirroring SNC ones. In this work, fibroblasts obtained from controls were studied after exposure to nonfibrillar Abeta 1-42, showing decreased glutamate uptake, similar to that observed in AD cells, in absence of transporters modifications. Nonfibrillar Abeta 1-42 was able to induce in control cells mitochondrial alterations and p38-phosphorylation, mirroring similar alterations found in AD fibroblasts. Under our experimental conditions, this treatment induced neither apoptosis nor necrosis. To investigate a putative role of p38-modulation in mediating nonfibrillar Abeta 1-42 toxicity, fibroblasts from controls were pretreated with retinoic-acid, and SB203580, a p38-inhibitor. These pretreatments prevented both p38-phosphorylation and glutamate uptake inhibition. Our results suggest that nonfibrillar Abeta 1-42 downregulates glutamate transporters activity interfering with p38-activation and mitochondrial stress. Thus, modulating complex kinase signaling pathway might represent a future therapeutic target in AD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.