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NF-κB/c-Rel deficiency causes Parkinson’s disease-like prodromal symptoms and progressive pathology in mice

Translational Neurodegeneration 2019年第1期8卷 183-202页

作者： Edoardo Parrella Arianna Bellucci vanessa porrini Marina Benarese Annamaria Lanzillotta Gaia Faustini Francesca Longhena Giulia Abate Daniela Uberti Marina Pizzi Department of Molecular and Translational Medicine University of BresciaViale Europa 1125123 BresciaItaly

Background:Parkinson’s disease(PD),the most common neurodegenerative movement disorder,is characterized by dopaminergic nigrostriatal neuron loss and brain accumulation of Lewy bodies,protein aggregates mainly composed ofα-*** reported that mice deficient for NF-κB/c-Rel(c-rel^(-/-))develop a late-onset *** 18 months of age,c-rel^(-/-)mice showed nigrostriatal degeneration and accumulation ofα-synuclein aggregates associated with a motor impairment responsive to L-DOPA *** c-Rel protein a transcriptional regulator for mitochondrial anti-oxidant and antiapoptotic factors,it has been inferred that its deficiency may affect the resilience of“energy demanding”nigral dopaminergic neurons to the aging *** patients manifest a prodromal syndrome that includes olfactory and gastrointestinal dysfunctions years before the frank degeneration of nigrostriatal neurons and appearance of motor *** to the Braak staging,the onset of non-motor and motor symptoms relates to progressive ascendant diffusion ofα-synuclein pathology in the *** aim of this study was to identify whether c-rel^(-/-)deficiency is associated with the onset of premotor signs of PD and spatio-temporal progression of cerebralα-synuclein ***:Intestinal and olfactory functions,intestine and brainα-synuclein deposition as well as striatal alterations,were assessed in c-rel^(-/-)and control mice from 2 to 18 months of ***:From 2 months of age,c-rel^(-/-)mice displayed intestinal constipation and increasing olfactory *** 2 months,c-rel^(-/-)mice exhibited a mildα-synuclein accumulation in the distal ***,they developed an agedependent deposition of fibrillaryα-synuclein that,starting at 5 months from the olfactory bulbs,dorsal motor nucleus of vagus and locus coeruleus,reached the substantia nigra at 12 *** this age,theα-synuclein pathology associated with a drop of dopamine transporter in the striatum tha

关键词： Parkinson’s disease NF-κB/c-Rel non-motor symptoms α-synuclein pathology progression

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