title: Gaucher-Associated Parkinsonism.
abstract: Gaucher disease is associated with Parkinson's disease (PD) by mutations in glucocerebrosidase (GCase). The gene encoding GCase, glucosidase beta acid (GBA), is an important risk factor for PD. Findings from large studies have shown that patients with PD have an increased frequency of mutations in GBA and that GBA mutation carriers exhibit diverse parkinsonian phenotypes and Lewy body pathology. Although the mechanism for this association remains elusive, some hypotheses have been proposed to explain it, including gain of function caused by GBA mutations, which increases α-synuclein (α-syn) aggregation, loss of function due to lysosomal enzyme deficiency, which affects α-syn clearance, and even a bidirectional feedback loop, but each of these hypotheses has its limitations. It is also worth noting that many findings have implicated the interaction between α-syn and GCase, indicating the essential role of the interaction in the pathogenesis of GBA-associated parkinsonism. Therefore, the current review focuses on α-syn and GCase, and it provides some new thoughts that may be helpful for understanding the α-syn-GCase interaction and unraveling the exact mechanism underlying GBA-associated parkinsonism.
authors.affiliation: Laboratory of Brain Function and Disease, Institute for Brain Sciences Research, School of Life Sciences, Henan University, Kaifeng, 475004, China.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Huimin
authors.initials: H
authors.lastname: Liang
authors.forename: Zhiquan
authors.initials: Z
authors.lastname: Zhao
authors.forename: Makoto
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Jianshe
authors.initials: J
authors.lastname: Wei
mesh_terms: D000818:Animals; D004843:Epistasis, Genetic; D005776:Gaucher Disease / Q000150:complications* / Q000235:genetics / Q000628:therapy; D005962:Glucosylceramidase / Q000235:genetics / Q000502:physiology; D006579:Heterozygote; D006801:Humans; D009154:Mutation / Q000502:physiology; D020734:Parkinsonian Disorders / Q000209:etiology* / Q000235:genetics / Q000628:therapy; D051844:alpha-Synuclein / Q000235:genetics
chemical_list: D051844:alpha-Synuclein; D005962:Glucosylceramidase
references.citation: Mol Genet Metab. 2003 Jun;79(2):104-9
references.pmid: 12809640
references.citation: Curr Opin Genet Dev. 2009 Jun;19(3):254-65
references.pmid: 19419854
references.citation: Hum Mutat. 2008 May;29(5):567-83
references.pmid: 18338393
references.citation: Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):12101-6
references.pmid: 21730160
references.citation: Mov Disord. 2005 Jan;20(1):100-3
references.pmid: 15517591
references.citation: Int J Cell Biol. 2011;2011:150450
references.pmid: 21760795
references.citation: Acta Neuropathol. 2010 Nov;120(5):641-9
references.pmid: 20838799
references.citation: Blood Cells Mol Dis. 2005 Nov-Dec;35(3):355-64
references.pmid: 16185900
references.citation: Front Neurol. 2012 Apr 27;3:65
references.pmid: 22557990
references.citation: J Geriatr Psychiatry Neurol. 2010 Dec;23(4):228-42
references.pmid: 20938043
references.citation: Blood Cells Mol Dis. 2006 May-Jun;36(3):426-8
references.pmid: 16651014
references.citation: Nat Med. 2014 Feb;20(2):204-8
references.pmid: 24441827
references.citation: Neuropharmacology. 2003 Jul;45(1):14-44
references.pmid: 12814657
references.citation: Cell Metab. 2013 Jun 4;17(6):941-53
references.pmid: 23707074
references.citation: Nat Genet. 1998 Feb;18(2):106-8
references.pmid: 9462735
references.citation: Curr Protein Pept Sci. 2009 Oct;10(5):483-99
references.pmid: 19538146
references.citation: Eur J Neurol. 2008 Apr;15 Suppl 1:14-20
references.pmid: 18353132
references.citation: Mov Disord. 2012 Apr;27(4):526-32
references.pmid: 22344629
references.citation: J Biomed Biotechnol. 2006;2006(3):78549
references.pmid: 17047314
references.citation: Blood Cells Mol Dis. 2011 Jan 15;46(1):95-102
references.pmid: 21067946
references.citation: Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15573-8
references.pmid: 25316793
references.citation: J Lipid Res. 2014 Oct;55(10):1996-2003
references.pmid: 24668939
references.citation: J Neurosci. 2004 Jul 28;24(30):6715-23
references.pmid: 15282274
references.citation: Arch Neurol. 2008 Mar;65(3):379-82
references.pmid: 18332251
references.citation: Exp Neurol. 2000 Dec;166(2):324-33
references.pmid: 11085897
references.citation: Science. 1997 Jun 27;276(5321):2045-7
references.pmid: 9197268
references.citation: Mov Disord. 2011 Aug 1;26(9):1593-604
references.pmid: 21618611
references.citation: Science. 2003 Oct 31;302(5646):841
references.pmid: 14593171
references.citation: Mov Disord. 2009 Aug 15;24(11):1571-8
references.pmid: 19425057
references.citation: Hum Mol Genet. 2011 Jan 1;20(1):202-10
references.pmid: 20947659
references.citation: Lancet. 2008 Oct 4;372(9645):1263-71
references.pmid: 19094956
references.citation: Brain. 2014 May;137(Pt 5):1304-22
references.pmid: 24531622
references.citation: Mol Genet Metab. 2011 Sep-Oct;104(1-2):185-8
references.pmid: 21742527
references.citation: J Neurol Neurosurg Psychiatry. 2009 Jun;80(6):667-70
references.pmid: 19448090
references.citation: J Biol Chem. 2011 Aug 12;286(32):28080-8
references.pmid: 21653695
references.citation: Ann Neurol. 2012 Sep;72(3):455-63
references.pmid: 23034917
references.citation: Brain. 2014 Mar;137(Pt 3):834-48
references.pmid: 24477431
references.citation: Neurology. 2011 Jul 19;77(3):276-80
references.pmid: 21734182
references.citation: J Neurol Neurosurg Psychiatry. 2012 Aug;83(8):853-4
references.pmid: 22577228
references.citation: Neurology. 2003 Jul 8;61(1):99-101
references.pmid: 12847165
references.citation: Am J Pathol. 2009 May;174(5):1891-909
references.pmid: 19349362
references.citation: Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3537-42
references.pmid: 23297226
references.citation: Parkinsonism Relat Disord. 2011 Jan;17(1):55-7
references.pmid: 20971030
references.citation: Cell. 2011 Jul 8;146(1):37-52
references.pmid: 21700325
references.citation: Ann Neurol. 2004 Feb;55(2):164-73
references.pmid: 14755719
references.citation: Science. 2004 Aug 27;305(5688):1292-5
references.pmid: 15333840
references.citation: Neurosci Lett. 2009 Mar 13;452(2):87-9
references.pmid: 19383421
references.citation: Brain. 2014 Aug;137(Pt 8):2303-11
references.pmid: 24919969
references.citation: Science. 2006 Jul 21;313(5785):324-8
references.pmid: 16794039
references.citation: Lancet Neurol. 2012 Nov;11(11):986-98
references.pmid: 23079555
references.citation: Hum Mol Genet. 2009 Apr 15;18(R1):R48-59
references.pmid: 19297401
references.citation: Hum Mol Genet. 2014 Feb 15;23(4):843-54
references.pmid: 24064337
references.citation: Brain. 2014 May;137(Pt 5):1481-95
references.pmid: 24574503
references.citation: Mol Genet Metab. 2013 Jan;108(1):56-64
references.pmid: 23266198
references.citation: Lancet. 2004 Sep 25-Oct 1;364(9440):1167-9
references.pmid: 15451224
references.citation: Mol Genet Metab. 2007 Jun;91(2):195-200
references.pmid: 17462935
references.citation: Neurosci Lett. 2010 Jan 22;469(2):256-9
references.pmid: 20004703
references.citation: Mov Disord. 2006 Dec;21(12):2062-7
references.pmid: 16991138
references.citation: Mol Genet Metab. 2004 Jul;82(3):192-207
references.pmid: 15234332
references.citation: Orphanet J Rare Dis. 2012;7:12
references.pmid: 22289779
references.citation: Mol Biol Cell. 2010 Jun 1;21(11):1850-63
references.pmid: 20392839
references.citation: Biochemistry. 2007 Feb 20;46(7):1868-77
references.pmid: 17253773
references.citation: J Med Genet. 2004 Dec;41(12):937-40
references.pmid: 15591280
references.citation: N Engl J Med. 2009 Oct 22;361(17):1651-61
references.pmid: 19846850
references.citation: Brain. 2009 Jul;132(Pt 7):1783-94
references.pmid: 19286695
references.citation: Blood Cells Mol Dis. 2007 May-Jun;38(3):287-93
references.pmid: 17196853
references.citation: Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3214-5
references.pmid: 23412333
references.citation: Neurology. 2008 Jun 10;70(24):2277-83
references.pmid: 18434642
references.citation: Arch Neurol. 2009 May;66(5):571-6
references.pmid: 19433656
references.citation: Mol Genet Metab. 2004 Jan;81(1):70-3
references.pmid: 14728994
references.citation: Trends Mol Med. 2011 Sep;17(9):485-93
references.pmid: 21723784