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ACS Chem Neurosci. 2017 Dec 20;8(12):2596-2606. doi: 10.1021/acschemneuro.7b00361. Epub 2017 Oct 25.

Genetic and Pharmacological Discovery for Alzheimer's Disease Using Caenorhabditis elegans.

Author information

1
Department of Biological Sciences, The University of Alabama , Tuscaloosa, Alabama 35487, United States.
2
Departments of Neurology and Neurobiology, Center for Neurodegeneration and Experimental Therapeutics, The University of Alabama School of Medicine at Birmingham , Birmingham, Alabama 35294, United States.

Abstract

The societal burden presented by Alzheimer's disease warrants both innovative and expedient means by which its underlying molecular causes can be both identified and mechanistically exploited to discern novel therapeutic targets and strategies. The conserved characteristics, defined neuroanatomy, and advanced technological application of Caenorhabditis elegans render this metazoan an unmatched tool for probing neurotoxic factors. In addition, its short lifespan and importance in the field of aging make it an ideal organism for modeling age-related neurodegenerative disease. As such, this nematode system has demonstrated its value in predicting functional modifiers of human neurodegenerative disorders. Here, we review how C. elegans has been utilized to model Alzheimer's disease. Specifically, we present how the causative neurotoxic peptides, amyloid-β and tau, contribute to disease-like neurodegeneration in C. elegans and how they translate to human disease. Furthermore, we describe how a variety of transgenic animal strains, each with distinct utility, have been used to identify both genetic and pharmacological modifiers of toxicity in C. elegans. As technological advances improve the prospects for intervention, the rapidity, unparalleled accuracy, and scale that C. elegans offers researchers for defining functional modifiers of neurodegeneration should speed the discovery of improved therapies for Alzheimer's disease.

KEYWORDS:

Aβ; Neurodegeneration; RNAi; genetics; screening; tau

PMID:
29022701
DOI:
10.1021/acschemneuro.7b00361
[Indexed for MEDLINE]

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