title: Impaired intracellular trafficking defines early Parkinson's disease.
abstract: 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 α-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.
authors: Oxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
authors: Benjamin H M
authors: BH
authors: Hunn
authors: Oxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
authors: Stephanie J
authors: SJ
authors: Cragg
authors: Oxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Medical Research Council Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
authors: J Paul
authors: JP
authors: Bolam
authors: Department of Clinical Neurosciences, University of Cambridge, The Clifford Allbutt Building, Hills Road, Cambridge CB2 0QH, UK.
authors: Maria-Grazia
authors: MG
authors: Spillantini
authors: Oxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK. Electronic address: richard.wade-martins@dpag.ox.ac.uk.
authors: Richard
authors: R
authors: Wade-Martins
mesh_terms: D000818:Animals; D001692:Biological Transport; D006801:Humans; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology
keywords: Parkinson's disease; Tau; cell trafficking; α-synuclein
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