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Review
. 2017 Jul 23;18(7):1596.
doi: 10.3390/ijms18071596.

Autophagy and Human Neurodegenerative Diseases-A Fly's Perspective

Myungjin Kim  1 , Allison Ho  2 , Jun Hee Lee  3
Affiliations
Review

Autophagy and Human Neurodegenerative Diseases-A Fly's Perspective

Myungjin Kim et al. Int J Mol Sci. .

Abstract

Neurodegenerative diseases in humans are frequently associated with prominent accumulation of toxic protein inclusions and defective organelles. Autophagy is a process of bulk lysosomal degradation that eliminates these harmful substances and maintains the subcellular environmental quality. In support of autophagy's importance in neuronal homeostasis, several genetic mutations that interfere with autophagic processes were found to be associated with familial neurodegenerative disorders. In addition, genetic mutations in autophagy-regulating genes provoked neurodegenerative phenotypes in animal models. The Drosophila model significantly contributed to these recent developments, which led to the theory that autophagy dysregulation is one of the major underlying causes of human neurodegenerative disorders. In the current review, we discuss how studies using Drosophila enhanced our understanding of the relationship between autophagy and neurodegenerative processes.

Keywords: Alzheimer; Drosophila; Huntington; Parkinson; ataxia; autophagy; mitochondrial dysfunction; neurodegeneration; protein aggregate.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Conserved autophagic processes between Drosophila and mammals. Red letters indicate that the gene and protein are associated with neurodegenerative diseases in humans. Red boxes indicate that the gene mutation and/or transgenic modulation can provoke neurodegeneration or neuronal dysfunction in the Drosophila system. Blue boxes indicate that, although the Drosophila gene is implicated in the autophagic process, its function in neuronal homeostasis has not been assessed. Thin arrows indicate signal flow, and thick arrows indicate the modification of complexes and vesicles. Blunted arrows indicate inhibition signals. The autophagosomal inner membrane and its contents are degraded after lysosomal fusion (dashed circle). pQ, polyglutamine tract; α-syn, α-synuclein; HTT, Huntingtin; Aβ, β-amyloid.
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References

    1. Ross C.A., Poirier M.A. Protein aggregation and neurodegenerative disease. Nat. Med. 2004;10:S10–S17. doi: 10.1038/nm1066. - DOI - PubMed
    1. Lin M.T., Beal M.F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 2006;443:787–795. doi: 10.1038/nature05292. - DOI - PubMed
    1. Ross C.A. Polyglutamine pathogenesis: Emergence of unifying mechanisms for huntington’s disease and related disorders. Neuron. 2002;35:819–822. doi: 10.1016/S0896-6273(02)00872-3. - DOI - PubMed
    1. Lesage S., Brice A. Parkinson’s disease: From monogenic forms to genetic susceptibility factors. Hum. Mol. Genet. 2009;18:R48–R59. doi: 10.1093/hmg/ddp012. - DOI - PubMed
    1. Feng Y., He D., Yao Z., Klionsky D.J. The machinery of macroautophagy. Cell Res. 2014;24:24–41. doi: 10.1038/cr.2013.168. - DOI - PMC - PubMed

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