Investigating the therapeutic potential of cannabidiol for Alzheimer’s disease: Using Caenorhabditis elegans that express the amyloid-beta protein

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Casmey, Kayleigh

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thesis

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eng

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C. elegans , Cannabidiol , Alzheimer's disease , Amyloid-beta

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Abstract

Roughly 55 million people worldwide suffer from dementia, and its prevalence is predicted to increase to about 139 million by 2050. Alzheimer’s disease (AD) is the most common form of dementia, accounting for 60-70% of cases. It is a progressive neurodegenerative disease characterized by various cognitive deficits beyond those associated with ageing. The prevailing hypothesis of AD pathology, the amyloid cascade hypothesis, assumes that the accumulation of the amyloid-beta (Aβ1–42 ) protein is the causative agent. AD has no cure and current treatments provide limited therapeutic benefits. Cannabidiol (CBD) is a cannabinoid derived from Cannabis plants that has neuroprotective, anti-inflammatory, and antioxidant properties. Research has shown its potential to help decrease Aβ production and protect against Aβ-mediated neurotoxicity in human cells. Further, CBD has been shown to reverse spatial memory deficits and prevent neuroinflammation from Aβ injection in rodent models. However, research on CBD as a treatment for AD is limited and the underlying mechanism is unclear. The model organism, Caenorhabditis elegans, is a well-established tool for studying human neurodegenerative diseases at a molecular level. A strain of C. elegans has been generated to express pan-neuronal Aβ1–42. This Aβ-expressing C. elegans has an age-related onset of dysfunction, including shortened lifespan and decreased locomotion, similar to what is observed in humans with AD. My research investigates the therapeutic potential of CBD and its mechanism in the Aβ-expressing C. elegans. Our findings support CBD as a therapeutic for AD and provide insight to how it is working. Results from our study will help fill the missing link between the effects of CBD on Aβ accumulation in AD and provide information on the role of CBD for AD treatment in humans.

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