Using Caenorhabditis elegans to fight human neurodegenerative diseases

Excerpt

Debilitating neurodegenerative disorders (NDs) including Alzheimer’s disease, Parkinson’s disease, and polyglutamine diseases are a major public health challenge in increasingly aging societies. Currently approved therapeutics are successful in slowing the progression of NDs but not in reversing or preventing the symptoms of NDs. The simplicity and amenability of the nematode Caenorhabditis elegans (C. elegans) to high-throughput genomic, proteomic and drug screening approaches make this organism an attractive choice for identifying new therapeutic compounds for these disorders and for understanding their mechanism of action. Indeed, a diverse set of informative C. elegans ND models have been developed manifesting abnormal behavioural or pathological phenotypes that partially recapitulate the salient cellular, molecular and pathological aspects of several distinct human NDs processes. Recent studies have identified dnajc5 encoding cysteine-string protein α (CSPα) as the disease-causing gene of a rare autosomal dominant human ND known as adult-onset neuronal ceroid lipofuscinosis (ANCL). The null animal models of CSP are characterised by impaired neurotransmission, pre-synaptic neurodegeneration and premature mortality. Simple model organisms may therefore shed light on potential therapeutic approaches for ANCL and other NDs. …