Changes in brain oxysterols at different stages of Alzheimer's disease: Their involvement in neuroinflammation
| العنوان: | Changes in brain oxysterols at different stages of Alzheimer's disease: Their involvement in neuroinflammation |
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| المؤلفون: | Luigi Iuliano, Gabriella Testa, Giuseppe Poli, Gabriella Leonarduzzi, Simona Gargiulo, Erica Staurenghi, Chiara Zerbinati, Fausto Fantò, Giorgio Giaccone, Paola Gamba |
| المصدر: | Redox Biology, Vol 10, Iss C, Pp 24-33 (2016) Redox Biology |
| بيانات النشر: | Elsevier BV, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 7α-OH, 7α-hydroxycholesterol, 0301 basic medicine, Clinical Biochemistry, COX-2, cyclooxigenase 2, CSF, cerebrospinal fluid, 7-OH-4-C, 7α-hydroxy-3-oxo-4-cholestenoic acid, 25-OH, 25-hydroxycholesterol, 0302 clinical medicine, Sirtuin 1, CYP27A1, polycyclic compounds, sirtuin-1, lcsh:QH301-705.5, lcsh:R5-920, biology, Chemistry, Proteolytic enzymes, Brain, Alzheimer's disease, cholesterol metabolism, inflammation, oxysterols, biochemistry, organic chemistry, 24-OH, 24-hydroxycholesterol, BBB, blood brain barrier, 7β-OH, 7β-hydroxycholesterol, SPE, solid phase extraction, Matrix Metalloproteinase 9, MCI, mild cognitive impairment, Disease Progression, MCP-1, monocyte chemotactic protein 1, Cholestanetriol 26-Monooxygenase, lipids (amino acids, peptides, and proteins), AD, Alzheimer's disease, lcsh:Medicine (General), Braak staging, Research Paper, Cholesterol metabolism, Inflammation, Oxysterols, Sirtuin-1, Aβ, amyloid β, medicine.medical_specialty, Oxysterol, 03 medical and health sciences, ROS, reactive oxygen species, PBS, phosphate buffered saline, 4β-OH, 4β-hydroxycholesterol, Alzheimer Disease, β-epoxy, 5β,6β-epoxycholesterol, Internal medicine, Cholesterol 24-Hydroxylase, medicine, SIRT-1, sirtuin 1, Humans, Cholesterol 24-hydroxylase, Liver X receptor, α-epoxy, 5α,6α-epoxycholesterol, p-tau, hyperphosphorylated tau, MMP-9, matrix metalloprotease 9, NFT, neurofibrillary tangles, medicine.disease, IL, interleukin, Oxidative Stress, 030104 developmental biology, Endocrinology, Gene Expression Regulation, lcsh:Biology (General), 27-OH, 27-hydroxycholesterol, Immunology, biology.protein, 7-K, 7-ketocholesterol, LXR, liver X receptor, 030217 neurology & neurosurgery |
| الوصف: | Alzheimer's disease (AD) is a gradually debilitating disease that leads to dementia. The molecular mechanisms underlying AD are still not clear, and at present no reliable biomarkers are available for the early diagnosis. In the last several years, together with oxidative stress and neuroinflammation, altered cholesterol metabolism in the brain has become increasingly implicated in AD progression. A significant body of evidence indicates that oxidized cholesterol, in the form of oxysterols, is one of the main triggers of AD. The oxysterols potentially most closely involved in the pathogenesis of AD are 24-hydroxycholesterol and 27-hydroxycholesterol, respectively deriving from cholesterol oxidation by the enzymes CYP46A1 and CYP27A1. However, the possible involvement of oxysterols resulting from cholesterol autooxidation, including 7-ketocholesterol and 7β-hydroxycholesterol, is now emerging. In a systematic analysis of oxysterols in post-mortem human AD brains, classified by the Braak staging system of neurofibrillary pathology, alongside the two oxysterols of enzymatic origin, a variety of oxysterols deriving from cholesterol autoxidation were identified; these included 7-ketocholesterol, 7α-hydroxycholesterol, 4β-hydroxycholesterol, 5α,6α-epoxycholesterol, and 5β,6β-epoxycholesterol. Their levels were quantified and compared across the disease stages. Some inflammatory mediators, and the proteolytic enzyme matrix metalloprotease-9, were also found to be enhanced in the brains, depending on disease progression. This highlights the pathogenic association between the trends of inflammatory molecules and oxysterol levels during the evolution of AD. Conversely, sirtuin 1, an enzyme that regulates several pathways involved in the anti-inflammatory response, was reduced markedly with the progression of AD, supporting the hypothesis that the loss of sirtuin 1 might play a key role in AD. Taken together, these results strongly support the association between changes in oxysterol levels and AD progression. Highlights • Changes in brain oxysterol levels may influence AD progression. • Oxysterol accumulation in the brain may amplify neuroinflammation. • SIRT-1 loss during AD progression may favor neuroinflammation. • Oxysterols and SIRT-1 might be useful markers for early AD diagnosis. |
| تدمد: | 2213-2317 |
| DOI: | 10.1016/j.redox.2016.09.001 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7a9b945552e34d8351be8658b3ef3a37 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7a9b945552e34d8351be8658b3ef3a37 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22132317 |
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| DOI: | 10.1016/j.redox.2016.09.001 |