Lipid-dependent deposition of alpha-synuclein and Tau on neuronal Secretogranin II-positive vesicular membranes with age

被引：26
作者：
Brekk, Oeystein R. [1 ]
Moskites, Alyssa [1 ]
Isacson, Ole [1 ]
Hallett, Penelope J. [1 ]
机构：
[1] Harvard Med Sch, McLean Hosp, Neuroregenerat Inst, Belmont, MA 02478 USA
来源：
SCIENTIFIC REPORTS | 2018年 / 8卷
关键词：
IN-VIVO; GLUCOCEREBROSIDASE MUTATIONS; CEREBROSPINAL-FLUID; PARKINSONS-DISEASE; ALZHEIMER-DISEASE; FATTY-ACIDS; MOUSE MODEL; DYSFUNCTION; OLIGOMERS; VESICLES;
D O I：
10.1038/s41598-018-33474-z
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
This report demonstrates insoluble alpha-synuclein (aSYN)+ aggregates in human sporadic Parkinson's disease (PD) midbrain that are linearly correlated with loss of glucocerebrosidase (GCase) activity. To identify early protein-lipid interactions that coincide with loss of lipid homeostasis, an aging study was carried out in mice with age-dependent reductions in GCase function. The analysis identified aberrant lipid-association by aSYN and hyperphosphorylated Tau (pTau) in a specific subset of neurotransmitter-containing, Secretogranin II (SgII)+ large, dense-core vesicles (LDCVs) responsible for neurotransmission of dopamine and other monoamines. The lipid vesicle-accumulation was concurrent with loss of PSD-95 suggesting synaptic destabilization. aSYN overexpression in the absence of lipid deregulation did not recapitulate the abnormal association with Sg II+ vesicles. These results show lipid-dependent changes occur with age in neuronal vesicular membrane compartments that accumulate lipid-stabilized aSYN and pTau.
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页数：11
相关论文
共 64 条
[1]   Discovery and characterization of stable and toxic Tau/phospholipid oligomeric complexes [J].
Ait-Bouziad, Nadine ;
Lv, Guohua ;
Mahul-Mellier, Anne-Laure ;
Xiao, Shifeng ;
Zorludemir, Gizem ;
Eliezer, David ;
Walz, Thomas ;
Lashuel, Hilal A. .
NATURE COMMUNICATIONS, 2017, 8
[2]   Beta-amyloid accumulation in APP mutant neurons reduces PSD-95 and GluR1 in synapses [J].
Almeida, CG ;
Tampellini, D ;
Takahashi, RH ;
Greengard, P ;
Lin, MT ;
Snyder, EM ;
Gouras, GK .
NEUROBIOLOGY OF DISEASE, 2005, 20 (02) :187-198
[3]   Sequential Extraction of Soluble and Insoluble Alpha-Synuclein from Parkinsonian Brains [J].
Bandopadhyay, Rina .
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2016, (107)
[4]   Alterations in the properties of the cell membrane due to glycosphingolipid accumulation in a model of Gaucher disease [J].
Batta, Gyula ;
Soltesz, Lilla ;
Kovacs, Tamas ;
Bozo, Tamas ;
Meszar, Zoltan ;
Kellermayer, Miklos ;
Szollosi, Janos ;
Nagy, Peter .
SCIENTIFIC REPORTS, 2018, 8
[5]   Neuropathology of older persons without cognitive impairment from two community-based studies [J].
Bennett, D. A. ;
Schneider, J. A. ;
Arvanitakis, Z. ;
Kelly, J. F. ;
Aggarwal, N. T. ;
Shah, R. C. ;
Wilson, R. S. .
NEUROLOGY, 2006, 66 (12) :1837-1844
[6]   Relation of neuropathology to cognition in persons without cognitive impairment [J].
Bennett, David A. ;
Wilson, Robert S. ;
Boyle, Patricia A. ;
Buchman, Aron S. ;
Schneider, Julie A. .
ANNALS OF NEUROLOGY, 2012, 72 (04) :599-609
[7]  
BRADY RO, 1965, J BIOL CHEM, V240, P39
[8]   α-Synuclein Promotes SNARE-Complex Assembly in Vivo and in Vitro [J].
Burre, Jacqueline ;
Sharma, Manu ;
Tsetsenis, Theodoros ;
Buchman, Vladimir ;
Etherton, Mark R. ;
Suedhof, Thomas C. .
SCIENCE, 2010, 329 (5999) :1663-1667
[9]   Comparative Lipidomic Analysis of Mouse and Human Brain with Alzheimer Disease [J].
Chan, Robin B. ;
Oliveira, Tiago G. ;
Cortes, Etty P. ;
Honig, Lawrence S. ;
Duff, Karen E. ;
Small, Scott A. ;
Wenk, Markus R. ;
Shui, Guanghou ;
Di Paolo, Gilbert .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (04) :2678-2688
[10]   A Progressive Mouse Model of Parkinson's Disease: The Thy1-aSyn ("Line 61") Mice [J].
Chesselet, Marie-Francoise ;
Richter, Franziska ;
Zhu, Chunni ;
Magen, Iddo ;
Watson, Melanie B. ;
Subramaniam, Sudhakar R. .
NEUROTHERAPEUTICS, 2012, 9 (02) :297-314
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