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Redox-active Cu(II)–Aβ causes substantial changes in axonal integrity in cultured cortical neurons in an oxidative-stress dependent manner

journal contribution
posted on 2023-05-17, 13:17 authored by Howells, C, Saar, K, Eaton, E, Shannon HuskinsShannon Huskins, Palumaa, P, Svetlana ShabalaSvetlana Shabala, Adlard, PA, William BennettWilliam Bennett, Adrian WestAdrian West, Guillemin, GJ, Chung, RS

Background: The beta-amyloid (Aβ) peptide comprises the amyloid plaques that characterise Alzheimer's disease (AD), and is thought to significantly contribute towards disease pathogenesis. Oxidative stress is elevated in the AD brain, and there is substantial evidence that the interaction between Aβ and redox-active copper is a major contributing factor towards oxidative stress in AD.

Results: The major findings of this study are that redox-active Cu(II)–Aβ causes pronounced axonal pathology in long-term neuronal cultures, including axonal fragmentation and the formation of hyperphosphorylated tau-immunoreactive axonal swellings. Notably, MAP-2 expressing dendritic processes remain largely un-affected by Cu(II)–Aβ treatment. These dystrophic axonal manifestations resemble some of the characteristic neuritic pathology of the AD brain. We show that Cu(II)–Aβ directly causes formation of intra-axonal swellings via the generation of free radicals and subsequent efflux of K+ out of neurons.

Conclusion: In summary, we report that redox-active Cu(II)–Aβ can induce substantial neurodegenerative changes in mature neurons, and may have an important role to play in the slowly progressing pathogenesis of AD.

History

Publication title

Experimental Neurology

Volume

237

Pagination

499-506

ISSN

0014-4886

Department/School

Menzies Institute for Medical Research

Publisher

Academic Press Inc Elsevier Science

Place of publication

525 B St, Ste 1900, San Diego, USA, Ca, 92101-4495

Rights statement

Copyright 2012 Elsevier

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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