Current and future implications of basic and translational research on amyloid-β peptide production and removal pathways
| Autor: | F-F Chen, Roger B. Dodd, Gerold Schmitt-Ulms, PH St George-Hyslop, Yi Li, Seema Qamar, Christopher Bohm, Jean Sevalle, Paul E. Fraser |
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| Rok vydání: | 2015 |
| Předmět: |
Amyloid
SORL1 Nicastrin Article Presenilin PICALM Translational Research Biomedical Cellular and Molecular Neuroscience Alzheimer Disease Next generation sequencing Genetics Amyloid precursor protein PSEN1 medicine Animals Humans Neurodegeneration Molecular Biology Amyloid beta-Peptides biology Cell Biology Secretase medicine.disease 3. Good health Alzheimer biology.protein Abeta Dementia Tau EPHA1 Alzheimer's disease APP Vaccine Amyloid precursor protein secretase APOE Signal Transduction |
| Zdroj: | Molecular and Cellular Neurosciences |
| ISSN: | 1044-7431 |
| DOI: | 10.1016/j.mcn.2015.02.016 |
| Popis: | Inherited variants in multiple different genes are associated with increased risk for Alzheimer's disease (AD). In many of these genes, the inherited variants alter some aspect of the production or clearance of the neurotoxic amyloid β-peptide (Aβ). Thus missense, splice site or duplication mutants in the presenilin 1 (PS1), presenilin 2 (PS2) or the amyloid precursor protein (APP) genes, which alter the levels or shift the balance of Aβ produced, are associated with rare, highly penetrant autosomal dominant forms of Familial Alzheimer's Disease (FAD). Similarly, the more prevalent late-onset forms of AD are associated with both coding and non-coding variants in genes such as SORL1, PICALM and ABCA7 that affect the production and clearance of Aβ. This review summarises some of the recent molecular and structural work on the role of these genes and the proteins coded by them in the biology of Aβ. We also briefly outline how the emerging knowledge about the pathways involved in Aβ generation and clearance can be potentially targeted therapeutically. This article is part of Special Issue entitled "Neuronal Protein". Highlights • Rare, medium and common variants in at least 20 genes are associated with AD. • Multiple genes affect processing of APP and production of Aβ peptide. • Others relate to immunity, inflammation, vesicular trafficking, and lipid metabolism. • These genes reflect steps in a complex metabolic/signalling cascade. • Nodal points in these pathways may represent potential therapeutic targets. |
| Databáze: | OpenAIRE |
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