Impaired intracellular trafficking defines early Parkinson's disease

被引：147

作者：

Hunn, Benjamin H. M. ^{[1
,2
]}

Cragg, Stephanie J. ^{[1
,2
]}

Bolam, J. Paul ^{[1
,3
]}

Spillantini, Maria-Grazia ^{[4
]}

Wade-Martins, Richard ^{[1
,2
]}

机构：

[1] Univ Oxford, Oxford Parkinsons Dis Ctr, Oxford OX1 3QX, England

[2] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England

[3] Univ Oxford, Dept Pharmacol, MRC, Anat Neuropharmacol Unit, Oxford OX1 3QT, England

[4] Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 0QH, England

来源：

TRENDS IN NEUROSCIENCES | 2015年 / 38卷 / 03期

基金：

英国医学研究理事会;

关键词：

Parkinson's disease; cell trafficking; Tau; alpha-synuclein; ALPHA-SYNUCLEIN OLIGOMERS; DOPAMINE NEURONS; INCREASED EXPRESSION; ECONOMIC-IMPACT; MOTOR PROTEINS; LRRK2; CONTROLS; MICE LACKING; MOUSE MODEL; MUTATIONS; GLUCOCEREBROSIDASE;

D O I：

10.1016/j.tins.2014.12.009

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Parkinson's disease (PD) is an insidious and incurable neurodegenerative disease, and represents a significant cost to individuals, carers, and ageing societies. It is defined at post-mortem by the loss of dopamine neurons in the substantia nigra together with the presence of Lewy bodies and Lewy neurites. We examine here the role of a-synuclein and other cellular transport proteins implicated in PD and how their aberrant activity may be compounded by the unique anatomy of the dopaminergic neuron. This review uses multiple lines of evidence from genetic studies, human tissue, induced pluripotent stem cells, and refined animal models to argue that prodromal PD can be defined as a disease of impaired intracellular trafficking. Dysfunction of the dopaminergic synapse heralds trafficking impairment.

引用

收藏

页码：178 / 188

页数：11

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