Effects of α-synuclein on axonal transport

NEUROBIOLOGY OF DISEASE

卷:105

Article

Volpicelli-Daley, Laura A.¹ 

[1] Univ Alabama Birmingham, Dept Neurol, Ctr Neurodegenerat & Expt Therapeut, Birmingham, AL 35294 USA

关键词: Axonal transport;    Synuclein;    Parkinson's disease;    Dementia with Lewy Bodies;    Lewy Bodies;    Lewy neurites;   

DOI  :  10.1016/j.nbd.2016.12.008

来源: Elsevier

【 摘 要 】

Lewy bodies and Lewy neurites composed primarily of alpha-synuclein characterize synucleinopathies including Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Despite decades of research on the impact of alpha-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 alpha-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. (C) 2016 Published by Elsevier Inc.

【 授权许可】

Free