Tau and Axonal Transport Misregulation in Tauopathies.

Abstract:

:Tau is a microtubule-associated protein that is involved in both normal and pathological processes in neurons. Since the discovery and characterization of tau over 40 years ago, our understanding of tau's normal functions and toxic roles in neurodegenerative tauopathies has continued to expand. Fast axonal transport is a critical process for maintaining axons and functioning synapses, critical subcellular compartments underlying neuronal connectivity. Signs of fast axonal transport disruption are pervasive in Alzheimer's disease and other tauopathies and various mechanisms have been proposed for regulation of fast axonal transport by tau. Post-translational modifications of tau including phosphorylation at specific sites, FTDP-17 point mutations, and oligomerization, confer upon tau a toxic effect on fast axonal transport. Consistent with the well-established dependence of axons on fast axonal transport, these disease-related modifications are closely associated temporally and spatially with axonal degeneration in the early disease stages. These factors position tau as a potentially critical factor mediating the disruption of fast axonal transport that precedes synaptic dysfunction and axonal degeneration at later disease stages. In this chapter, we review the evidence that tau affects fast axonal transport and examine several potential mechanisms proposed to underlie this toxicity.

journal_name

Adv Exp Med Biol

authors

Combs B,Mueller RL,Morfini G,Brady ST,Kanaan NM

doi

10.1007/978-981-32-9358-8_7

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

81-95

eissn

0065-2598

issn

2214-8019

journal_volume

1184

pub_type

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