Review

Modulating macroautophagy: a neuronal perspective

Christopher W Johnson

Department of Neurology, College of Physician & Surgeons, Columbia University, NY, USA

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Thomas J Melia

Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA

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Ai Yamamoto

* Author for correspondence

Department of Neurology, College of Physician & Surgeons, Columbia University, NY, USA.

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Email the corresponding author at ay46@columbia.edu

Published Online:28 Aug 2012https://doi.org/10.4155/fmc.12.112

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Abstract

Over this past decade, macroautophagy has gained prominence in the field of adult-onset neurodegeneration: from sporadic disorders such as Alzheimer’s and Parkinson’s disease, to genetic disorders such as Huntington’s disease and frontotemporal dementia, the influence of this fundamental pathway has become an important topic of discussion. While there has been particular emphasis on the potential benefits of macroautophagy, there is growing literature that also suggests that macroautophagy contributes towards neurotoxicity. In this review, we discuss the molecular mechanism of macroautophagy and the currently available pharmacological tools, with special emphasis on mammalian macroautophagy in adult brain. Studies indicate that neuronal context strongly influences the role macroautophagy plays in maintaining cellular health, reflecting an ongoing need for better understanding of how macroautophagic regulation is achieved in the heavily differentiated and polarized neurons if we are to effectively manipulate it to treat neurodegenerative disease.

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Published online 28 August 2012

Published in print September 2012

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Acknowledgements

The authors would like to thank J Dragich and A Simonsen for careful reading of this manuscript.

Financial & competing interests disclosure

This work was supported by the NINDS RO1 NS063973, NINDS RO1 NS077111 (A Yamamoto) and the Parkinson’s Disease Foundation (A Yamamoto). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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