title: Spreading of α-synuclein in the face of axonal transport deficits in Parkinson's disease: a speculative synthesis.
abstract: Parkinson's disease (PD) is mainly attributed to degeneration of dopamine neurons in the substantia nigra, but its etiopathogenesis also includes impaired protein clearance and axonal transport dysfunction, among others. The spread of α-synuclein (α-syn) aggregates from one neuron to another, in a prion-like manner, is hypothesized to contribute to PD progression. Axonal transport is likely to play a crucial role in this movement of α-syn aggregates between brain regions. At the same time, deficits in axonal transport are suggested to contribute to neuronal failure in PD. In this review, we discuss the apparent contradiction that axonal transport might be essential for disease progression, while dysfunction of axonal transport could simultaneously be a cornerstone of PD pathogenesis. We speculate around models that reconcile how axonal transport can play such a paradoxical role.
authors.affiliation: Laboratory for Translational Parkinson's Disease Research, Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA.
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: Lamberts
authors.affiliation: Laboratory for Translational Parkinson's Disease Research, Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA.
authors.forename: Erin N
authors.initials: EN
authors.lastname: Hildebrandt
authors.affiliation: Laboratory for Translational Parkinson's Disease Research, Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA; Neuronal Survival Unit, Wallenberg Neuroscience Center, Lund University, Lund, Sweden. Electronic address: patrik.brundin@vai.org.
authors.forename: Patrik
authors.initials: P
authors.lastname: Brundin
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D006801:Humans; D028361:Mitochondrial Diseases / Q000209:etiology; D009457:Neuroglia / Q000502:physiology; D010300:Parkinson Disease / Q000150:complications* / Q000473:pathology*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein
keywords: Alphaherpesvirus; Braak staging; Microglia; Mitochondria; Oligodendrocytes; Prion-like