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

Isabella A Silveira, Adam S Mullis, Dana M Cairns, Anna Shevzov-Zebrun, Jordyn Whalen, Alexa Galuppo, Katherine G Walsh, David L Kaplan

Journal: Free radical biology & medicine 2022;186():76-92

PMID: 35537596

Full Text on Elsevier Science View on PubMed

Abstract

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.

Address: Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.; Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA; Allen Discovery Center, Tufts University, Medford, MA, 02155, USA.; Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA; Allen Discovery Center, Tufts University, Medford, MA, 02155, USA. Electronic address: [email protected].

DOI: 10.1016/j.freeradbiomed.2022.05.002

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MeSH Terms: Alzheimer Disease, Cognitive Dysfunction, Gliosis, Humans, Neuroprotective Agents, Plaque, Amyloid