Howells, C and Saar, K and Eaton, E and Ray, S and Palumaa, P and Shabala, L and Adlard, PA and Bennett, WR and West, AK and Guillemin, GJ and Chung, RS, Redox-active Cu(II)-Aβ causes substantial changes in axonal integrity in cultured cortical neurons in an oxidative-stress dependent manner, Experimental Neurology, 237, (2) pp. 499-506. ISSN 0014-4886 (2012) [Refereed Article]
Copyright 2012 Elsevier
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)ľAβ 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)ľAβ treatment. These dystrophic axonal manifestations resemble some of the characteristic neuritic pathology of the AD brain. We show that Cu(II)ľAβ 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)ľAβ can induce substantial neurodegenerative changes in mature neurons, and may have an important role to play in the slowly progressing pathogenesis of AD.
|Item Type:||Refereed Article|
|Keywords:||neurodegeneration, beta-amyloid, neurotoxicity, oxidative stress, axon degeneration|
|Research Division:||Medical and Health Sciences|
|Research Field:||Central Nervous System|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Nervous System and Disorders|
|UTAS Author:||Howells, C (Ms Claire Howells)|
|UTAS Author:||Eaton, E (Dr Emma Eaton)|
|UTAS Author:||Ray, S (Mrs Shannon Huskins)|
|UTAS Author:||Shabala, L (Associate Professor Lana Shabala)|
|UTAS Author:||Bennett, WR (Dr Bill Bennett)|
|UTAS Author:||West, AK (Professor Adrian West)|
|UTAS Author:||Chung, RS (Associate Professor Roger Chung)|
|Web of Science® Times Cited:||4|
|Deposited By:||Menzies Institute for Medical Research|
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