Caenorhabditis elegans as an emerging high throughput chronotherapeutic drug screening platform for human neurodegenerative disorders

Abstract

An increase in the aging population is accompanied by increased susceptibility to age-associated neurodegeneration, with currently no cure. Despite the diversity of symptoms and etiologies, neurodegenerative disorders share mechanistic commonalities and many pathophysiological features. These include disruptions in circadian rhythms that affect neuronal physiology. Systematic investigations in several animal models have advanced our understanding of the molecular processes that link circadian rhythms and neurodegenerative disease states. These models have also been used to screen and validate promising chronotherapeutic drug candidates that target the circadian clock to ameliorate neurodegeneration. With the emergence of robust and reliable methodologies to measure daily rhythms, the nematode model Caenorhabditis elegans has become a versatile tool for high throughput chronotherapeutic drug screening against neurodegenerative disorders. In this review, we discuss the unique features and advantages of C. elegans as an enabling platform for chronotherapeutic drug discovery, towards the development of innovative strategies for the treatment of human neurodegenerative conditions.