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Peptides. 2014 Dec;62:197-202. doi: 10.1016/j.peptides.2014.09.018. Epub 2014 Sep 30.

Alpha synuclein is transported into and out of the brain by the blood-brain barrier.

Author information

1
Department of Pathology, University of Washington School of Medicine, 325 9th Ave, HMC Box 359635, Seattle, WA 98104, United States.
2
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.
3
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.

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.

KEYWORDS:

Alpha-synuclein; Blood–brain barrier; LRP-1; Parkinson's disease; p-Glycoprotein

PMID:
25278492
PMCID:
PMC4378645
DOI:
10.1016/j.peptides.2014.09.018
[Indexed for MEDLINE]
Free PMC Article

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