title: Exosomes in the Pathology of Neurodegenerative Diseases.
abstract: More than 30 years ago, two unexpected findings were discovered that challenged conventional thinking in biology. The first was the identification of a misfolded protein with transmissible properties associated with a group of neurodegenerative diseases known as transmissible spongiform encephalopathies. The second was the discovery of a new pathway used for the extracellular release of biomolecules, including extracellular vesicles called exosomes. Two decades later, the convergence of these pathways was shown when exosomes were found to play a significant role in both the transmission and propagation of protein aggregates in disease. Recent research has now revealed that the majority of proteins involved in neurodegenerative diseases are transported in exosomes, and that external stresses due to age-related impairment of protein quality control mechanisms can promote the transcellular flux of these proteins in exosomes. Significantly, exosomes provide an environment that can induce the conformational conversion of native proteins into aggregates that can be transmitted to otherwise aggregate-free cells in the brain. Here we review the current roles of exosomes in the pathology of neurodegenerative diseases.
authors.affiliation: From the Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3010 and jason.howitt@florey.edu.au.
authors.forename: Jason
authors.initials: J
authors.lastname: Howitt
authors.affiliation: the Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria 3086, Australia andrew.hill@latrobe.edu.au.
authors.forename: Andrew F
authors.identifier: http://orcid.org/0000-0001-5581-2354
authors.initials: AF
authors.lastname: Hill
mesh_terms: D000818:Animals; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology*
keywords: Alzheimer disease; Parkinson disease; exosomes; extracellular vesicles; prion; prion disease