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Use of Caenorhabditis elegans as a model to study Alzheimer's disease and other neurodegenerative diseases.

ABSTRACT: Advances in research and technology has increased our quality of life, allowed us to combat diseases, and achieve increased longevity. Unfortunately, increased longevity is accompanied by a rise in the incidences of age-related diseases such as Alzheimer's disease (AD). AD is the sixth leading cause of death, and one of the leading causes of dementia amongst the aged population in the USA. It is a progressive neurodegenerative disorder, characterized by the prevalence of extracellular A? plaques and intracellular neurofibrillary tangles, derived from the proteolysis of the amyloid precursor protein (APP) and the hyperphosphorylation of microtubule-associated protein tau, respectively. Despite years of extensive research, the molecular mechanisms that underlie the pathology of AD remain unclear. Model organisms, such as the nematode, Caenorhabditis elegans, present a complementary approach to addressing these questions. C. elegans has many advantages as a model system to study AD and other neurodegenerative diseases. Like their mammalian counterparts, they have complex biochemical pathways, most of which are conserved. Genes in which mutations are correlated with AD have counterparts in C. elegans, including an APP-related gene, apl-1, a tau homolog, ptl-1, and presenilin homologs, such as sel-12 and hop-1. Since the neuronal connectivity in C. elegans has already been established, C. elegans is also advantageous in modeling learning and memory impairments seen during AD. This article addresses the insights C. elegans provide in studying AD and other neurodegenerative diseases. Additionally, we explore the advantages and drawbacks associated with using this model.

SUBMITTER: Alexander AG

PROVIDER: S-EPMC4155875 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Use of Caenorhabditis elegans as a model to study Alzheimer's disease and other neurodegenerative diseases.

Alexander Adanna G AG Marfil Vanessa V Li Chris C

Frontiers in genetics 20140905

Advances in research and technology has increased our quality of life, allowed us to combat diseases, and achieve increased longevity. Unfortunately, increased longevity is accompanied by a rise in the incidences of age-related diseases such as Alzheimer's disease (AD). AD is the sixth leading cause of death, and one of the leading causes of dementia amongst the aged population in the USA. It is a progressive neurodegenerative disorder, characterized by the prevalence of extracellular Aβ plaques ...[more]

PMID: 25250042

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Project description:Emerging evidence from both clinical studies and animal models indicates the importance of the interaction between the gut microbiome and the brain in the pathogenesis of neurodegenerative diseases (NDs). Although how microbes modulate neurodegeneration is still mostly unclear, recent studies have started to probe into the mechanisms for the communication between microbes and hosts in NDs. In this review, we highlight the advantages of using Caenorhabditis elegans (C. elegans) to disentangle the microbe-host interaction that regulates neurodegeneration. We summarize the microbial pro- and anti-neurodegenerative factors identified using the C. elegans ND models and the effects of many are confirmed in mouse models. Specifically, we focused on the role of bacterial amyloid proteins, such as curli, in promoting proteotoxicity and neurodegeneration by cross-seeding the aggregation of endogenous ND-related proteins, such as α-synuclein. Targeting bacterial amyloid production may serve as a novel therapeutic strategy for treating NDs, and several compounds, such as epigallocatechin-3-gallate (EGCG), were shown to suppress neurodegeneration at least partly by inhibiting curli production. Because bacterial amyloid fibrils contribute to biofilm formation, inhibition of amyloid production often leads to the disruption of biofilms. Interestingly, from a list of 59 compounds that showed neuroprotective effects in C. elegans and mouse ND models, we found that about half of them are known to inhibit bacterial growth or biofilm formation, suggesting a strong correlation between the neuroprotective and antibiofilm activities. Whether these potential therapeutics indeed protect neurons from proteotoxicity by inhibiting the cross-seeding between bacterial and human amyloid proteins awaits further investigations. Finally, we propose to screen the long list of antibiofilm agents, both FDA-approved drugs and novel compounds, for their neuroprotective effects and develop new pharmaceuticals that target the gut microbiome for the treatment of NDs. To this end, the C. elegans ND models can serve as a platform for fast, high-throughput, and low-cost drug screens that target the microbe-host interaction in NDs.

Dataset Information

Use of Caenorhabditis elegans as a model to study Alzheimer's disease and other neurodegenerative diseases.

Publications

Use of Caenorhabditis elegans as a model to study Alzheimer's disease and other neurodegenerative diseases.

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