title: Effects of α-synuclein on axonal transport.
abstract: Lewy bodies and Lewy neurites composed primarily of α-synuclein characterize synucleinopathies including Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Despite decades of research on the impact of α-synuclein, little is known how abnormal inclusion made of this protein compromise neuronal function. Emerging evidence suggests that defects in axonal transport caused by aggregated α-synuclein contribute to neuronal dysfunction. These defects appear to occur well before the onset of neuronal death. Susceptible neurons in PD such as dopamine neurons with long elaborate axons may be particularly sensitive to abnormal axonal transport. Axonal transport is critical for delivery of signaling molecules to the soma responsible for neuronal differentiation and survival. In addition, axonal transport delivers degradative organelles such as endosomes and autophagosomes to lysosomes located in the soma to degrade damaged proteins and organelles. Identifying the molecular mechanisms by which axonal transport is impaired in PD and DLB may help identify novel therapeutic targets to enhance neuron survival and even possibly prevent disease progression. Here, we review the evidence that axonal transport is impaired in synucleinopathies, and describe potential mechanisms by which contribute to these defects.
authors.affiliation: Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: lvolpicellidaley@uabmc.edu.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Volpicelli-Daley
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D006801:Humans; D020961:Lewy Body Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein
keywords: Axonal transport; Dementia with Lewy Bodies; Lewy Bodies; Lewy neurites; Parkinson's disease; Synuclein