title: The secret life of extracellular vesicles in metal homeostasis and neurodegeneration.
abstract: Biologically active metals such as copper, zinc and iron are fundamental for sustaining life in different organisms with the regulation of cellular metal homeostasis tightly controlled through proteins that coordinate metal uptake, efflux and detoxification. Many of the proteins involved in either uptake or efflux of metals are localised and function on the plasma membrane, traffic between intracellular compartments depending upon the cellular metal environment and can undergo recycling via the endosomal pathway. The biogenesis of exosomes also occurs within the endosomal system, with several major neurodegenerative disease proteins shown to be released in association with these vesicles, including the amyloid-β (Aβ) peptide in Alzheimer's disease and the infectious prion protein involved in Prion diseases. Aβ peptide and the prion protein also bind biologically active metals and are postulated to play important roles in metal homeostasis. In this review, we will discuss the role of extracellular vesicles in Alzheimer's and Prion diseases and explore their potential contribution to metal homeostasis.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC, Australia.|Bio21 Molecular Science and Biotechnology Institute, Parkville, VIC, Australia.
authors.forename: Shayne A
authors.initials: SA
authors.lastname: Bellingham
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC, Australia.|Bio21 Molecular Science and Biotechnology Institute, Parkville, VIC, Australia.
authors.forename: Belinda
authors.initials: B
authors.lastname: Guo
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC, Australia.|Bio21 Molecular Science and Biotechnology Institute, Parkville, VIC, Australia.|Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, Australia.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Hill
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D000067128:Extracellular Vesicles / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D008670:Metals / Q000378:metabolism*; D017096:Prion Diseases / Q000378:metabolism*
chemical_list: D008670:Metals
keywords: Exosomes; Intercellular communication; Metal homeostasis; Microvesicles; Neurodegeneration