title: Alpha synuclein is transported into and out of the brain by the blood-brain barrier.
abstract: Alpha-synuclein (α-Syn), a small protein with multiple physiological and pathological functions, is one of the dominant proteins found in Lewy Bodies, a pathological hallmark of Lewy body disorders, including Parkinson's disease (PD). More recently, α-Syn has been found in body fluids, including blood and cerebrospinal fluid, and is likely produced by both peripheral tissues and the central nervous system. Exchange of α-Syn between the brain and peripheral tissues could have important pathophysiologic and therapeutic implications. However, little is known about the ability of α-Syn to cross the blood-brain barrier (BBB). Here, we found that radioactively labeled α-Syn crossed the BBB in both the brain-to-blood and the blood-to-brain directions at rates consistent with saturable mechanisms. Low-density lipoprotein receptor-related protein-1 (LRP-1), but not p-glycoprotein, may be involved in α-Syn efflux and lipopolysaccharide (LPS)-induced inflammation could increase α-Syn uptake by the brain by disrupting the BBB.
authors.affiliation: Department of Pathology, University of Washington School of Medicine, 325 9th Ave, HMC Box 359635, Seattle, WA 98104, United States.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Sui
authors.affiliation: Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Room 810 Bldg 1, 1660 S. Columbian Way, Seattle, WA 98108, United States.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Bullock
authors.affiliation: Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Room 810 Bldg 1, 1660 S. Columbian Way, Seattle, WA 98108, United States.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Erickson
authors.affiliation: Department of Pathology, University of Washington School of Medicine, 325 9th Ave, HMC Box 359635, Seattle, WA 98104, United States.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Room 810 Bldg 1, 1660 S. Columbian Way, Seattle, WA 98108, United States; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, United States. Electronic address: wabanks1@uw.edu.
authors.forename: W A
authors.initials: WA
authors.lastname: Banks
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000401:mortality* / Q000473:pathology; D016631:Lewy Bodies / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008077:Lipoproteins, LDL; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D051379:Mice; D010300:Parkinson Disease / Q000378:metabolism* / Q000503:physiopathology; D011973:Receptors, LDL / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C486645:Lrp1 protein, mouse; D011973:Receptors, LDL; D025521:Tumor Suppressor Proteins; D051844:alpha-Synuclein
keywords: Alpha-synuclein; Blood–brain barrier; LRP-1; Parkinson's disease; p-Glycoprotein