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Axonal Transport Defects in Alzheimer’s Disease

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Abstract

A large body of evidences indicates that axonal transport (AT) defects play an important role in the pathogenesis of Alzheimer’ disease (AD). AT, a critical cellular process for the maintenance and function of a neuron, requires components of the cytoskeletons as “tracks”, motor proteins and ATP as “driving force”, adaptor proteins to ensure the specific connection of the transported cargoes and motor proteins as well as active regulation. In AD pathology, AD-linked pathologic factors respectively perturb the four basic components of AT through different signaling pathways to cause AT defects. Mitochondrial transport, which is different from other transport cargoes, is also impaired via special pathways in AD. In this paper, we review the inhibitory effects of those factors on AT and their possible pathways, indicating these factors act in overlapping, synergistic, and circulating ways. Given the contributions of AT defects to AD, recent therapeutic studies focus on microtubule-stabilizing (MT-stabilizing) agents and alteration in phosphotransferase activities, and we propose more therapeutic strategies targeting AT defects.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81000544, 81171209, 81371406) and Shandong Provincial Natural Science Foundation, China (ZR2010HQ004, ZR2011HZ001).

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The authors declare no conflicts of interest.

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  1. Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China

    Zi-Xuan Wang, Lan Tan & Jin-Tai Yu

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  1. Zi-Xuan Wang
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Correspondence to Lan Tan or Jin-Tai Yu.

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Wang, ZX., Tan, L. & Yu, JT. Axonal Transport Defects in Alzheimer’s Disease. Mol Neurobiol 51, 1309–1321 (2015). https://doi.org/10.1007/s12035-014-8810-x

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