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Folding for the Synapse pp 257–267Cite as

Synaptic Dysfunction in Parkinson’s Disease: From Protein Misfolding to Functional Alterations

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Abstract

Neurodegenerative disorders are devastating human diseases that include Parkinson’s, Huntington’s and Alzheimer’s disease, amyotrophic lateral sclerosis, and the frontal temporal dementias. Although the clinical manifestations of these disorders have been known for some time, our understanding of the molecular underpinnings is only starting to emerge. Protein misfolding and aggregation is a common hallmark among these diseases, and these events are likely to produce a number of cellular and functional alterations. In Parkinson’s disease (PD), alpha-synuclein misfolds and forms intracellular inclusions known as Lewy bodies (LBs). Accumulating evidence suggests that these events lead to the disruption of intracellular trafficking which will, undoubtedly, lead to defects in synaptic transmission. Dysfunction in the basal ganglia circuitry is strongly associated with PD, with loss of dopaminergic neurons in the substantia nigra. Here, we present an overview of how misfolding and aggregation of alpha-­synuclein might be related to synaptic dysfunction in PD. A deeper understanding of the molecular basis of PD will enable us to devise novel strategies for therapeutic intervention which may be applied to several neurodegenerative disorders that seem to have similar roots.

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Acknowledgements

TFO is supported by the Michael J. Fox Foundation, Calouste Gulbenkian Foundation, Fundação para a Ciência e Tecnologia and by a Marie Curie International Reintegration Grant from the European Commission. LVL is supported by Fundação para a Ciência e Tecnologia.

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  1. Cell and Molecular Neuroscience Unit, Instituto de Medicina Molecular, Av. Prof. Egas Moniz, 1649-028, Lisboa, Portugal

    Tiago Fleming Outeiro

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  1. Tiago Fleming Outeiro
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  2. Luísa Vaqueiro Lopes
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Correspondence to Tiago Fleming Outeiro .

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  1. School of Biological Sciences, University of Southampton, Life Science Building (B85), SO17 1BJ, Southampton, SO16 7PX, United Kingdom

    Andreas Wyttenbach

  2. School of Biological Sciences, University of Southampton, Life Science Building (B85), SO17 1BJ, Southampton, SO16 7PX, United Kingdom

    Vincent O'Connor

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Outeiro, T.F., Lopes, L.V. (2011). Synaptic Dysfunction in Parkinson’s Disease: From Protein Misfolding to Functional Alterations. In: Wyttenbach, A., O'Connor, V. (eds) Folding for the Synapse. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-7061-9_13

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