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Omata, Y., Lim, Y.M., Akao, Y., Tsuda, L. (2014). Age-induced reduction of autophagy-related gene expression is associated with onset of Alzheimer's disease.  Am. J. Neurodegener. Dis. 3(3): 134--142.
FlyBase ID
FBrf0227410
Publication Type
Research paper
Abstract

Aging is a major risk factor for Alzheimer's disease (AD). Aggregation of amyloid beta (Aβ) in cerebral cortex and hippocampus is a hallmark of AD. Many factors have been identified as causative elements for onset and progression of AD; for instance, tau seems to mediate the neuronal toxicity of Aβ, and downregulation of macroautophagy (autophagy) is thought to be a causative element of AD pathology. Expression of autophagy-related genes is reduced with age, which leads to increases in oxidative stress and aberrant protein accumulation. In this study, we found that expression of the autophagy-related genes atg1, atg8a, and atg18 in Drosophila melanogaster was regulated with aging as well as their own activities. In addition, the level of atg18 was maintained by dfoxo (foxo) and dsir2 (sir2) activities in concert with aging. These results indicate that some autophagy-related gene expression is regulated by foxo/sir2-mediated aging processes. We further found that reduced autophagy activity correlated with late-onset neuronal dysfunction caused by neuronal induction of Aβ. These data support the idea that age-related dysfunction of autophagy is a causative element in onset and progression of AD.

PubMed ID
PubMed Central ID
PMC4299720 (PMC) (EuropePMC)
DOI
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Am. J. Neurodegener. Dis.
    Title
    American journal of neurodegenerative disease
    ISBN/ISSN
    2165-591X
    Data From Reference
    Aberrations (2)
    Alleles (10)
    Genes (8)
    Human Disease Models (1)
    Natural transposons (1)
    Experimental Tools (2)
    Transgenic Constructs (7)