4.7 Article

Screening neuroprotective compounds in herpes-induced Alzheimer?s disease cell and 3D tissue models

Journal

FREE RADICAL BIOLOGY AND MEDICINE
Volume 186, Issue -, Pages 76-92

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2022.05.002

Keywords

Alzheimer?s disease; 3D culture; Bioengineering; Screening

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This study used 2D and 3D tissue culture models to investigate herpesvirus-induced Alzheimer's Disease (AD). Screening 21 medications, supplements, and nutraceuticals, the researchers found that green tea catechins and resveratrol showed strong anti-plaque properties and neuroprotective benefits, making them potential candidates for further investigation in AD prevention and therapies.
Alzheimer's Disease (AD) is a neurodegenerative disorder that can cause life-altering and debilitating cognitive decline. AD's etiology is poorly understood, and no disease-modifying therapeutics exist. Here, we describe the use of 2D and 3D tissue culture models of herpesvirus-induced AD, which recapitulate hallmark disease features of plaque formation, gliosis, neuroinflammation, and impaired neuronal signaling, to screen a panel of 21 medications, supplements, and nutraceuticals with purported neuroprotective benefits. This screen identified green tea catechins and resveratrol as having strong anti-plaque properties, functional neuroprotective benefits, and minimal neurotoxicity, providing support for their further investigation as AD preventives and therapies. Two other candidates, citicoline and metformin, reduced plaque formation and were minimally toxic, but did not protect against virus-induced impairments in neuronal signaling. This study establishes a simple platform for rapidly screening and characterizing AD compounds of interest in 2D and 3D human cortical tissue models representing physiologically relevant disease features.

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