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 Aβ 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.

Coconut (Cocos nucifera) Ethanolic Leaf Extract Reduces Amyloid-β (1-42) Aggregation and Paralysis Prevalence in Transgenic Caenorhabditis elegans Independently of Free Radical Scavenging and Acetylcholinesterase Inhibition

“…To this end, nematodes have been utilized in pathway analysis and drug screening for diseases such as AD, Parkinson’s disease (PD), and Huntington’s (HD) [32,33,34]. Further, the conservation of 12 over 17 signalling cascades, a short generation time, and a life cycle of two to three weeks, as well as the ease of observation provided by its transparent body lining, provide efficient tools for scoring protein aggregation [35].…”

Alzheimer’s disease: experimental models and reality

“…Overall, the sequence homology in genes of interest in AD is minimal between invertebrates and humans and these invertebrate orthologues often lack regions of these genes that are important in AD pathophysiology. The most notable example is the lack of Aβ in Drosophila and C. Elegans [1, 38]. Therefore, invertebrates cannot be considered to model AD without genetic manipulation to express human transgenes of APP, Aβ and/or tau.…”

“…Therefore, invertebrates cannot be considered to model AD without genetic manipulation to express human transgenes of APP, Aβ and/or tau. One of the main advantages of using invertebrates is the ease of genetic manipulation and multiple transgenic lines expressing human APP, Aβ and tau have been developed for each species [1, 38, 111]. Other general advantages of using invertebrate models include easy handling, low cost and short life span of animals.…”

The promises of neurodegenerative disease modeling

“…The nematode C. elegans offers a number of advantages including a transparent body, a simple and very well defined nervous system and the possibility to carry out extensive forward and reverse genetic screens. It has proved to be a very useful organism for the study of proteinopathy and aging and various models for Alzheimer's disease, Huntington's disease, Parkinson's disease, Amyotrophic lateral sclerosis, taupathies and fronto temporal dementia have been modeled in this organism [4,16,24,25].…”

“…A brief overview only of the major results obtained in recent years with these models will be given here and the reader is referred to excellent recent reviews for more detailed accounts on the progress made in modelling specific diseases [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18].…”