{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T19:14:33Z","timestamp":1778181273673,"version":"3.51.4"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations in DJ-1 (encoded by PARK7) are a very rare cause of early-onset recessive Parkinson\u2019s disease. We describe a patient with early-onset parkinsonism, starting at the age of 22, with poor response to levodopa and additional features in progression (dystonia, pyramidal signs and dementia), who died when he was 49 years old. The neuropathological study showed severe substantia nigra and locus coeruleus neuronal loss, with diffuse Lewy body pathology (Lewy bodies, aberrant neurites, grain-like structures, spheroids and scattered glial pathology). Genetic analysis revealed a novel c.515T &amp;gt; A; p.L172Q mutation in the PARK7 gene. To evaluate the pathogenicity of this new mutation we explored DJ-1 expression levels in vitro showing a massive reduction in DJ-1 protein levels due to a highly unstable and rapidly degraded L172Q mutant. DJ-1 immunohistochemistry of brain tissue revealed no staining in our case. This is the first neuropathological report of a brain from DJ-1-linked parkinsonism that, although based on a single case study, suggests that DJ-1 mutations are causative of \u03b1-synucleinopathy. These results can help in the understanding of Parkinson\u2019s disease pathophysiology, promote research studies to increase the knowledge on the pathways involved in the neurodegeneration process, and pave the way for new therapeutic interventions.<\/jats:p>","DOI":"10.1093\/brain\/aww080","type":"journal-article","created":{"date-parts":[[2016,4,17]],"date-time":"2016-04-17T00:18:12Z","timestamp":1460852292000},"page":"1680-1687","source":"Crossref","is-referenced-by-count":110,"title":["DJ-1 linked parkinsonism (PARK7) is associated with Lewy body pathology"],"prefix":"10.1093","volume":"139","author":[{"given":"Ricardo","family":"Taipa","sequence":"first","affiliation":[{"name":"Portuguese Brain Bank, Neuropathology Unit, Centro Hospitalar do Porto, Porto, Portugal"}]},{"given":"Concei\u00e7\u00e3o","family":"Pereira","sequence":"first","affiliation":[{"name":"UnIGENe, IBMC, Institute for Molecular and Cell Biology, and Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, Porto, Portugal"}]},{"given":"In\u00eas","family":"Reis","sequence":"first","affiliation":[{"name":"Portuguese Brain Bank, Neuropathology Unit, Centro Hospitalar do Porto, Porto, Portugal"}]},{"given":"Isabel","family":"Alonso","sequence":"first","affiliation":[{"name":"UnIGENe, IBMC, Institute for Molecular and Cell Biology, and Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, Porto, Portugal"}]},{"given":"Ant\u00f3nio","family":"Bastos-Lima","sequence":"first","affiliation":[{"name":"Department of Neurology, Centro Hospitalar do Porto, Porto, Portugal"}]},{"given":"Manuel","family":"Melo-Pires","sequence":"first","affiliation":[{"name":"Portuguese Brain Bank, Neuropathology Unit, Centro Hospitalar do Porto, Porto, Portugal"}]},{"given":"Marina","family":"Magalh\u00e3es","sequence":"first","affiliation":[{"name":"Department of Neurology, Centro Hospitalar do Porto, Porto, Portugal"}]}],"member":"286","published-online":{"date-parts":[[2016,4,16]]},"reference":[{"key":"2020071611552531900_aww080-B1","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/ana.10675","article-title":"The role of pathogenic DJ-1 mutations in Parkinson's disease","volume":"54","author":"Abou-Sleiman","year":"2003","journal-title":"Ann Neurol"},{"key":"2020071611552531900_aww080-B2","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1002\/ana.20666","article-title":"DJ-1 mutations and parkinsonism-dementia-amyotrophic lateral sclerosis complex","volume":"58","author":"Annesi","year":"2005","journal-title":"Ann Neurol"},{"key":"2020071611552531900_aww080-B3","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1093\/brain\/awh054","article-title":"The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson's disease","volume":"127","author":"Bandopadhyay","year":"2004","journal-title":"Brain"},{"key":"2020071611552531900_aww080-B4","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/ana.10106","article-title":"Localization of autosomal recessive early-onset parkinsonism to chromosome 1p36 (PARK7) in an independent dataset","volume":"51","author":"Bonifati","year":"2002","journal-title":"Ann Neurol"},{"key":"2020071611552531900_aww080-B5","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1126\/science.1077209","article-title":"Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism","volume":"299","author":"Bonifati","year":"2003","journal-title":"Science"},{"key":"2020071611552531900_aww080-B6","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s00401-006-0127-z","article-title":"Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry","volume":"112","author":"Braak","year":"2006","journal-title":"Acta Neuropathol"},{"key":"2020071611552531900_aww080-B7","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0197-4580(02)00065-9","article-title":"Staging of brain pathology related to sporadic Parkinson's disease","volume":"24","author":"Braak","year":"2003","journal-title":"Neurobiol Aging"},{"key":"2020071611552531900_aww080-B8","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.brainresbull.2008.08.014","article-title":"Intralaminar nuclei of the thalamus in Lewy body diseases","volume":"78","author":"Brooks","year":"2009","journal-title":"Brain Res Bull"},{"key":"2020071611552531900_aww080-B9","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1212\/WNL.54.5.21A","article-title":"Prevalence of Parkinson's disease in Europe: a collaborative study of population-based cohorts. 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