Abstract
Ageing is the greatest risk factor for the development of Parkinson's disease. However, the current dogma holds that cellular mechanisms that are associated with ageing of midbrain dopamine neurons and those that are related to dopamine neuron degeneration in Parkinson's disease are unrelated. We propose, based on evidence from studies of non-human primates, that normal ageing and the degeneration of dopamine neurons in Parkinson's disease are linked by the same cellular mechanisms and, therefore, that markers of cellular risk factors accumulate with age in a pattern that mimics the pattern of degeneration observed in Parkinson's disease. We contend that ageing induces a pre-parkinsonian state, and that the cellular mechanisms of dopamine neuron demise during normal ageing are accelerated or exaggerated in Parkinson's disease through a combination of genetic and environmental factors.
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Acknowledgements
We are grateful for the dedication and effort of all members of our investigative teams and the generous support provided by the US National Institutes of Health (NIH) awards AG10851 and NS58830 (to the Udall Center of Excellence in Parkinson's Disease Research at Michigan State University, USA).
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J.H.K. is a founding scientist with a financial interest in Ceregene Inc., USA.
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Glossary
- Lipofuscin
-
Autofluorescent lipid-containing residues of lysosomal digestion that accumulate in many tissues of the body with advancing age and have been termed 'age pigment'.
- Neuromelanin
-
A modified form of melanin pigment found in dopamine neurons of the substantia nigra.
- Probenicid
-
An adjuvant that, when co-administered with MPTP, blocks rapid clearance of the toxin and its metabolites, producing a progressive rodent model of parkinsonism.
- Synucleinopathy
-
An abnormal structure or quantity of α-synuclein that disrupts the function of cells.
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Collier, T., Kanaan, N. & Kordower, J. Ageing as a primary risk factor for Parkinson's disease: evidence from studies of non-human primates. Nat Rev Neurosci 12, 359–366 (2011). https://doi.org/10.1038/nrn3039
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DOI: https://doi.org/10.1038/nrn3039
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