RGD Reference Report - Impaired intracellular trafficking defines early Parkinson's disease. - Rat Genome Database

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Impaired intracellular trafficking defines early Parkinson's disease.

Authors: Hunn, BH  Cragg, SJ  Bolam, JP  Spillantini, MG  Wade-Martins, R 
Citation: Hunn BH, etal., Trends Neurosci. 2015 Mar;38(3):178-88. doi: 10.1016/j.tins.2014.12.009. Epub 2015 Jan 29.
RGD ID: 10450521
Pubmed: PMID:25639775   (View Abstract at PubMed)
PMCID: PMC4740565   (View Article at PubMed Central)
DOI: DOI:10.1016/j.tins.2014.12.009   (Journal Full-text)

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 alpha-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.


Molecular Pathway Annotations    Click to see Annotation Detail View
Objects Annotated

Genes (Rattus norvegicus)
Dnajc6  (DnaJ heat shock protein family (Hsp40) member C6)
Gba1  (glucosylceramidase beta 1)
Lrrk2  (leucine-rich repeat kinase 2)
Pink1  (PTEN induced kinase 1)
Prkn  (parkin RBR E3 ubiquitin protein ligase)
Snca  (synuclein alpha)
Synj1  (synaptojanin 1)
Vps35  (VPS35 retromer complex component)

Genes (Mus musculus)
Dnajc6  (DnaJ heat shock protein family (Hsp40) member C6)
Gba1  (glucosylceramidase beta 1)
Lrrk2  (leucine-rich repeat kinase 2)
Pink1  (PTEN induced putative kinase 1)
Prkn  (parkin RBR E3 ubiquitin protein ligase)
Snca  (synuclein, alpha)
Synj1  (synaptojanin 1)
Vps35  (VPS35 retromer complex component)

Genes (Homo sapiens)
DNAJC6  (DnaJ heat shock protein family (Hsp40) member C6)
GBA1  (glucosylceramidase beta 1)
LRRK2  (leucine rich repeat kinase 2)
PINK1  (PTEN induced kinase 1)
PRKN  (parkin RBR E3 ubiquitin protein ligase)
SNCA  (synuclein alpha)
SYNJ1  (synaptojanin 1)
VPS35  (VPS35 retromer complex component)


Additional Information