title: Metals and Neuronal Metal Binding Proteins Implicated in Alzheimer's Disease.
abstract: Alzheimer's disease (AD) is the most prevalent age-related dementia affecting millions of people worldwide. Its main pathological hallmark feature is the formation of insoluble protein deposits of amyloid-β and hyperphosphorylated tau protein into extracellular plaques and intracellular neurofibrillary tangles, respectively. Many of the mechanistic details of this process remain unknown, but a well-established consequence of protein aggregation is synapse dysfunction and neuronal loss in the AD brain. Different pathways including mitochondrial dysfunction, oxidative stress, inflammation, and metal metabolism have been suggested to be implicated in this process. In particular, a body of evidence suggests that neuronal metal ions such as copper, zinc, and iron play important roles in brain function in health and disease states and altered homeostasis and distribution as a common feature across different neurodegenerative diseases and aging. In this focused review, we overview neuronal proteins that are involved in AD and whose metal binding properties may underlie important biochemical and regulatory processes occurring in the brain during the AD pathophysiological process.
authors.affiliation: Faculdade de Ciências Universidade de Lisboa, Biosystems and Integrative Sciences Institute and Department of Chemistry and Biochemistry, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal.
authors.forename: Joana S
authors.identifier: 0000-0003-3833-0016
authors.initials: JS
authors.lastname: Cristóvão
authors.affiliation: Development of the Nervous System, Institut de Biologie de l'Ecole Normale Supérieure (IBENS), INSERM U1024, CNRS UMR8197, 46 rue d'Ulm, 75005 Paris, France.
authors.forename: Renata
authors.identifier: 0000-0002-3085-5128
authors.initials: R
authors.lastname: Santos
authors.affiliation: Faculdade de Ciências Universidade de Lisboa, Biosystems and Integrative Sciences Institute and Department of Chemistry and Biochemistry, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal.
authors.forename: Cláudio M
authors.identifier: 0000-0003-4662-6933
authors.initials: CM
authors.lastname: Gomes
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D008670:Metals / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D066329:Protein Aggregates
chemical_list: D000682:Amyloid; D002352:Carrier Proteins; D008670:Metals; D066329:Protein Aggregates