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http://hdl.handle.net/2445/140074
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DC Field | Value | Language |
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dc.contributor.author | Hou, Xu | - |
dc.contributor.author | Fiesel, Fabienne C. | - |
dc.contributor.author | Truban, Dominika | - |
dc.contributor.author | Castanedes Casey, Monica | - |
dc.contributor.author | Lin, Wen-lang | - |
dc.contributor.author | Soto, Alexandra I. | - |
dc.contributor.author | Tacik, Pawel | - |
dc.contributor.author | Rousseau, Linda G. | - |
dc.contributor.author | Diehl, Nancy N. | - |
dc.contributor.author | Heckman, Michael G. | - |
dc.contributor.author | Lorenzo-Betancor, Oswaldo | - |
dc.contributor.author | Ferrer, Isidro (Ferrer Abizanda) | - |
dc.contributor.author | Arbelo, José M. | - |
dc.contributor.author | Steele, John C. | - |
dc.contributor.author | Farrer, Matthew J. | - |
dc.contributor.author | Cornejo-Olivas, Maria | - |
dc.contributor.author | Torres, Luis | - |
dc.contributor.author | Mata, Ignacio F. | - |
dc.contributor.author | Graff-Radford, Neill R. | - |
dc.contributor.author | Wszolek, Zbigniew K. | - |
dc.contributor.author | Ross, Owen A. | - |
dc.contributor.author | Murray, Melissa E. | - |
dc.contributor.author | Dickson, Dennis W. | - |
dc.contributor.author | Springer, Wolfdieter | - |
dc.date.accessioned | 2019-09-16T13:52:12Z | - |
dc.date.available | 2019-09-16T13:52:12Z | - |
dc.date.issued | 2018-08-01 | - |
dc.identifier.issn | 1554-8627 | - |
dc.identifier.uri | http://hdl.handle.net/2445/140074 | - |
dc.description.abstract | Although exact causes of Parkinson disease (PD) remain enigmatic, mitochondrial dysfunction is increasingly appreciated as a key determinant of dopaminergic neuron susceptibility in both familial and sporadic PD. Two genes associated with recessive, early-onset PD encode the ubiquitin (Ub) kinase PINK1 and the E3 Ub ligase PRKN/PARK2/Parkin, which together orchestrate a protective mitochondrial quality control (mitoQC) pathway. Upon stress, both enzymes cooperatively identify and decorate damaged mitochondria with phosphorylated poly-Ub (p-S65-Ub) chains. This specific label is subsequently recognized by autophagy receptors that further facilitate mitochondrial degradation in lysosomes (mitophagy). Here, we analyzed human post-mortem brain specimens and identified distinct pools of p-S65-Ub-positive structures that partially colocalized with markers of mitochondria, autophagy, lysosomes and/or granulovacuolar degeneration bodies. We further quantified levels and distribution of the 'mitophagy tag' in 2 large cohorts of brain samples from normal aging and Lewy body disease (LBD) cases using unbiased digital pathology. Somatic p-S65-Ub structures independently increased with age and disease in distinct brain regions and enhanced levels in LBD brain were age- and Braak tangle stage-dependent. Additionally, we observed significant correlations of p-S65-Ub with LBs and neurofibrillary tangle levels in disease. The degree of co-existing p-S65-Ub signals and pathological PD hallmarks increased in the pre-mature stage, but decreased in the late stage of LB or tangle aggregation. Altogether, our study provides further evidence for a potential pathogenic overlap among different forms of PD and suggests that p-S65-Ub can serve as a biomarker for mitochondrial damage in aging and disease. | - |
dc.format.extent | 15 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Landes Bioscience | - |
dc.relation.isformatof | Versió postprint del document publicat a: https://doi.org/10.1080/15548627.2018.1461294 | - |
dc.relation.ispartof | Autophagy, 2018, vol. 14, num. 8, p. 1404-1418 | - |
dc.relation.uri | https://doi.org/10.1080/15548627.2018.1461294 | - |
dc.rights | (c) Landes Bioscience , 2018 | - |
dc.source | Articles publicats en revistes (Patologia i Terapèutica Experimental) | - |
dc.subject.classification | Envelliment | - |
dc.subject.classification | Autofàgia | - |
dc.subject.classification | Mitocondris | - |
dc.subject.classification | Malaltia de Parkinson | - |
dc.subject.classification | Ubiqüitina | - |
dc.subject.other | Aging | - |
dc.subject.other | Autophagy | - |
dc.subject.other | Mitochondria | - |
dc.subject.other | Parkinson's disease | - |
dc.subject.other | Ubiquitin | - |
dc.title | Age- and disease-dependent increase of the mitophagy marker phospho-ubiquitin in normal aging and Lewy body disease | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/acceptedVersion | - |
dc.identifier.idgrec | 689453 | - |
dc.date.updated | 2019-09-16T13:52:12Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 29947276 | - |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) |
Files in This Item:
File | Description | Size | Format | |
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689453.pdf | 11.65 MB | Adobe PDF | View/Open |
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