{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:52:18Z","timestamp":1786978338262,"version":"build-2736575974"},"reference-count":129,"publisher":"Wiley","issue":"1-2","license":[{"start":{"date-parts":[[2013,12,20]],"date-time":"2013-12-20T00:00:00Z","timestamp":1387497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics Clinical Apps"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:p>Down syndrome (DS) is one of the most common genetic causes of intellectual disability characterized by multiple pathological phenotypes, among which neurodegeneration is a key feature. The neuropathology of DS is complex and likely results from impaired mitochondrial function, increased oxidative stress, and altered proteostasis. After the age of 40 years, many (most) DS individuals develop a type of dementia that closely resembles that of Alzheimer's disease with deposition of senile plaques and neurofibrillary tangles. A number of studies demonstrated that increased oxidative damage, accumulation of damaged\/misfolded protein aggregates, and dysfunction of intracellular degradative systems are critical events in the neurodegenerative processes. This review summarizes the current knowledge that demonstrates a \u201cchronic\u201d condition of oxidative stress in DS pointing to the putative molecular pathways that could contribute to accelerate cognition and memory decline. Proteomics and redox proteomics studies are powerful tools to unravel the complexity of DS phenotypes, by allowing to identifying protein expression changes and oxidative PTMs that are proved to be detrimental for protein function. It is reasonable to suggest that changes in the cellular redox status in DS neurons, early from the fetal period, could provide a fertile environment upon which increased aging favors neurodegeneration. Thus, after a critical age, DS neuropathology can be considered a human model of early Alzheimer's disease and could contribute to understanding the overlapping mechanisms that lead from normal aging to development of dementia.<\/jats:p>","DOI":"10.1002\/prca.201300066","type":"journal-article","created":{"date-parts":[[2013,11,20]],"date-time":"2013-11-20T09:12:02Z","timestamp":1384938722000},"page":"73-85","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Unraveling the complexity of neurodegeneration in brains of subjects with Down syndrome: Insights from proteomics"],"prefix":"10.1002","volume":"8","author":[{"given":"Marzia","family":"Perluigi","sequence":"first","affiliation":[{"name":"Department of Biochemical Sciences Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Di Domenico","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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