Evidence for autophagic gridlock in aging and neurodegeneration

Mathieu F. Bakhoum, Christine Y. Bakhoum, Zhixia Ding, Susan M Carlton, Gerald A. Campbell, George R. Jackson

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Autophagy is essential to neuronal homeostasis, and its impairment is implicated in the development of neurodegenerative pathology. However, the underlying mechanisms and consequences of this phenomenon remain a matter of conjecture. We show that misexpression of human tau in Drosophila induces accumulation of autophagic intermediates with a preponderance of large vacuoles, which we term giant autophagic bodies (GABs), which are reminiscent of dysfunctional autophagic entities. Lowering basal autophagy reduces GABs, whereas increasing autophagy decreases mature autolysosomes. Induction of autophagy is also associated with rescue of the tauopathy phenotype, suggesting that formation of GABs may be a compensatory mechanism rather than a trigger of neurodegeneration. Last, we show that the peculiar Biondi bodies observed in the choroid epithelium of both elderly and Alzheimer's disease human brains express immunoreactive markers similar to those of GABs. Collectively, these data indicate that autophagic gridlock contributes to the development of pathology in aging and neurodegeneration.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalTranslational Research
Volume164
Issue number1
DOIs
StatePublished - Jul 2014

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Biochemistry, medical
  • Physiology (medical)

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    Bakhoum, M. F., Bakhoum, C. Y., Ding, Z., Carlton, S. M., Campbell, G. A., & Jackson, G. R. (2014). Evidence for autophagic gridlock in aging and neurodegeneration. Translational Research, 164(1), 1-12. https://doi.org/10.1016/j.trsl.2014.01.016