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Life Extension pp 191–211Cite as

Protein Quality Control in Brain Aging: Lessons from Protein Misfolding Disorders in Drosophila

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Part of the book series: Healthy Ageing and Longevity ((HAL,volume 3))

Abstract

Protein quality control is an essential process for cellular survival. When protein damage occurs, a series of coordinated response mechanisms repair or degrade damaged proteins to avoid the accumulation of toxic protein aggregates and restore proteostasis. However, the amount of misfolded proteins increases during aging overwhelming the mechanisms responsible for protein quality control, thus leading to the development of several age-dependent neurodegenerative disorders. Interestingly, targeted expression of proteins causative of these diseases in flies reproduces the pathological behaviors seen in humans. This remarkable conservation provides a valuable experimental tool to elucidate the complex mechanisms associated with the maintenance of proteostasis. In this chapter, we summarize how Drosophila has contributed to understand the roles of the heat shock response, the unfolded protein response, autophagy and the ubiquitin proteasome system in brain aging and neurodegeneration associated with protein-misfolding disorders. In addition, we describe fundamental contributions of the fly system to the design of new therapeutic strategies for these devastating disorders.

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Acknowledgments

We apologize to all authors whose work could not be cited due to space constraints. This work was supported in part by NIH grant R21NS081356 to DER-L, and by a McKnight Brain Institute Research Development Award and start-up funds from the UF Department of Neurology to PF-F and DER-L.

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Authors and Affiliations

  1. Department of Neurology, McKnight Brain Institute, Florida, USA

    Lorena de Mena, Pedro Fernandez-Funez & Diego E. Rincon-Limas

  2. Department of Neuroscience, Genetics Institute, and Center for Translational Research in Neurodegenerative Disease, University of Florida, 1149 Newell Dr, Gainesville, FL, 32611, USA

    Pedro Fernandez-Funez & Diego E. Rincon-Limas

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  1. Lorena de Mena
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  2. Pedro Fernandez-Funez
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  3. Diego E. Rincon-Limas
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Correspondence to Pedro Fernandez-Funez or Diego E. Rincon-Limas .

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Editors and Affiliations

  1. Laboratory of Epigenetics, Institute of Gerontology, Kiev, Kievs'ka, Ukraine

    Alexander M. Vaiserman

  2. Laboratory of Molecular Radiobiology and Gerontology, Institute of Biology of Komi Science Center of Ural Branch of RAS, Syktyvkar, Komi Republic, Russia

    Alexey A. Moskalev

  3. Laboratory of Genome Variation, Institute of Molecular Genetics of RAS, Moscow, Russia

    Elena G. Pasyukova

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de Mena, L., Fernandez-Funez, P., Rincon-Limas, D.E. (2015). Protein Quality Control in Brain Aging: Lessons from Protein Misfolding Disorders in Drosophila . In: Vaiserman, A., Moskalev, A., Pasyukova, E. (eds) Life Extension. Healthy Ageing and Longevity, vol 3. Springer, Cham. https://doi.org/10.1007/978-3-319-18326-8_8

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