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81.
A prion, a protease-resistant conformer of the cellular prion protein (PrP(C)), is the causative agent of transmissible spongiform encephalopathies or prion diseases. While this property is well established for the aberrantly folded protein, the physiological function of PrP(C) remains elusive. Among different putative functions, the non-pathogenic protein isoform PrP(C) is involved in several cellular processes. Here, we show that PrP(C) regulates the cleavage of neuregulin-1 proteins (NRG1). Neuregulins provide key axonal signals that regulate several processes, including glial cells proliferation, survival and myelination. Interestingly, mice devoid of PrP(C) (Prnp?/?) were recently shown to have a late-onset demyelinating disease in the peripheral nervous system (PNS) but not in the central nervous system (CNS). We found that NRG1 processing is developmentally regulated in the PNS and, by comparing wildtype and Prnp?/? mice, that PrP(C) influences NRG1 processing in old, but not in young, animals. In addition, we found that also the processing of neuregulin-3, another neuregulin family member, is altered in the PNS of Prnp?/? mice. These differences in neuregulin proteins processing are not paralleled in the CNS, thus suggesting a different cellular function for PrP(C) between the CNS and the PNS. 相似文献
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Friedman J Roze E Abdenur JE Chang R Gasperini S Saletti V Wali GM Eiroa H Neville B Felice A Parascandalo R Zafeiriou DI Arrabal-Fernandez L Dill P Eichler FS Echenne B Gutierrez-Solana LG Hoffmann GF Hyland K Kusmierska K Tijssen MA Lutz T Mazzuca M Penzien J Poll-The BT Sykut-Cegielska J Szymanska K Thöny B Blau N 《Annals of neurology》2012,71(4):520-530
86.
Familial amyloid polyneuropathies (FAP) constitute a group of inherited amyloidoses that affect peripheral nerves. One common form of FAP is caused by transthyretin (TTR) misfolding and deposition in the peripheral nervous system, leading to neuronal toxicity and death. The molecular mechanisms responsible for this toxicity are unclear; however, there is good biochemical and histopathological evidence that the toxicity of TTR mutations is correlated to their aggregation state. In addition, neuronal calcium dysregulation is a mechanism that has been suggested to drive the pathogenesis of FAP. Amyloidogenic TTR mutations cause significant calcium influx via L-type calcium channels in neuronal cell lines, while in primary sensory neurons, TTR mediates a calcium influx via a novel mechanism of transient receptor potential melanostatin (TRPM8) and voltage-gated sodium and calcium channel activation. Significantly, calcium dysregulation is a pathological hallmark of other neurodegenerative diseases involving amyloidosis, for example Alzheimer's disease, and this mechanism could explain the molecular events that drive amyloid toxicity in other neurodegenerative diseases. 相似文献
87.
Francesca Furlan Attilio Rovelli Miriam Rigoldi Mirella Filocamo Barbara Tappino Douglas Friday Serena Gasperini Silvana Mariani Claudia Izzi Maria Pia Bondioni Cinzia Gellera Anna Venerando Nicoletta Villa Maria del Carmen Rodriguez Perez Fabio Pavan Andrea Biondi Rossella Parini 《Italian journal of pediatrics》2018,44(2):128
88.
M Cosimelli R Golfieri P P Cagol L Carpanese R Sciuto C L Maini R Mancini I Sperduti G Pizzi M G Diodoro M Perrone E Giampalma B Angelelli F Fiore S Lastoria S Bacchetti D Gasperini O Geatti F Izzo 《British journal of cancer》2010,103(3):324-331
Background:
This multi-centre phase II clinical trial is the first prospective evaluation of radioembolisation of patients with colorectal liver metastases (mCRC) who failed previous oxaliplatin- and irinotecan-based systemic chemotherapy regimens.Methods:
Eligible patients had adequate hepatic, haemopoietic and renal function, and an absence of major hepatic vascular anomalies and hepato-pulmonary shunting. Gastroduodenal and right gastric arteries were embolised before hepatic arterial administration of yttrium-90 resin microspheres (median activity, 1.7 GBq; range, 0.9–2.2).Results:
Of 50 eligible patients, 38 (76%) had received ⩾4 lines of chemotherapy. Most presented with synchronous disease (72%), >4 hepatic metastases (58%), 25–50% replacement of total liver volume (60%) and bilateral spread (70%). Early and intermediate (>48 h) WHO G1–2 adverse events (mostly fever and pain) were observed in 16 and 22% of patients respectively. Two died due to renal failure at 40 days or liver failure at 60 days respectively. By intention-to-treat analysis using Response Evaluation Criteria in Solid Tumours, 1 patient (2%) had a complete response, 11 (22%) partial response, 12 (24%) stable disease, 22 (44%) progressive disease; 4 (8%) were non-evaluable. Median overall survival was 12.6 months (95% CI, 7.0–18.3); 2-year survival was 19.6%.Conclusion:
Radioembolisation produced meaningful response and disease stabilisation in patients with advanced, unresectable and chemorefractory mCRC. 相似文献89.
G Antonelli E Simeoni F Bagnato C Pozzilli O Turriziani R Tesoro P Di Marco C Gasperini C Fieschi F Dianzani 《Journal of the neurological sciences》1999,168(2):131-136
The development of neutralizing antibodies (NAbs) to interferon (IFN) is a common phenomenon of IFN beta therapy for relapsing-remitting multiple sclerosis (RRMS) patients. Here we examine the specificity of NAbs developed during therapy for RRMS with recombinant interferon (rIFN) beta-1a or rIFN beta-1b, and study the effect of switching from rIFN beta-1a to rIFN beta-1b on the incidence and specificity of NAbs. The relative ability to neutralize rIFN beta-1a and beta-1b was assayed in sera positive for NAbs derived from RRMS patients treated with either rIFN beta-1a (N=9) or rIFN beta-1b (N=16), while the incidence and specificity of NAbs to IFN beta developed during therapy were studied in 50 RRMS patients who were treated for two years with rIFN beta-1a followed by a further year either switching to rIFN beta-1b (N=34) or continuing treatment with rIFN beta-1a (N=16). The results show that all positive sera, independent of the source, may recognize both forms of rIFN beta and that a further year of treatment does not significantly affect the incidence and specificity of the NAbs developed during the first two years of treatment even if treatment is switched to a different type of IFN beta. The data then suggests that it is unlikely that the administration of rIFN beta-1b to anti-rIFN beta-1a NAbs-positive patients can overcome the inhibitory effect exerted by the serum antibodies (and vice versa), and that a further period of treatment with IFN beta-1b in patients previously treated with rIFN beta-1a does not significantly change the pattern of antibody response to IFN beta. 相似文献
90.
de Sitter Alexandra Verhoeven Tom Burggraaff Jessica Liu Yaou Simoes Jorge Ruggieri Serena Palotai Miklos Brouwer Iman Versteeg Adriaan Wottschel Viktor Ropele Stefan Rocca Mara A. Gasperini Claudio Gallo Antonio Yiannakas Marios C. Rovira Alex Enzinger Christian Filippi Massimo De Stefano Nicola Kappos Ludwig Frederiksen Jette L. Uitdehaag Bernard M. J. Barkhof Frederik Guttmann Charles R. G. Vrenken Hugo 《Journal of neurology》2020,267(12):3541-3554
Journal of Neurology - Deep grey matter (DGM) atrophy in multiple sclerosis (MS) and its relation to cognitive and clinical decline requires accurate measurements. MS pathology may deteriorate the... 相似文献