Catechins and resveratrol from green tea neuroprotective for patients with herpes-induced AD

Using 2D and 3D human cortical tissue models that replicate physiologically significant disease characteristics, Isabella Silveira and colleagues have demonstrated a straightforward framework for quickly screening and identifying Alzheimer's Disease (AD) drugs of interest. This study was published in Free Radical Biology and Medicine.

An incapacitating and life-altering cognitive decline can result from Alzheimer's disease, a neurodegenerative condition. There are no treatments that can change the course of AD, and its origin is poorly known. The purpose of this study was to evaluate a panel of 21 drugs, dietary supplements, and nutraceuticals for their potential to provide neuroprotective benefits. The researchers used 2D and 3D tissue culture models of herpesvirus-induced AD, which recapitulate hallmark disease features such as plaque formation, neuroinflammation, gliosis, and impaired neuronal signaling.

Human foreskin fibroblasts were used to direct reprogram human-induced neural stem cells (hiNSCs). HSV-1 was introduced into these cells at a multiplicity of infection (MOI) of 0.0001. Models of the human cortical brain tissue in 3D were created. Viral inoculums were combined with experimental substances. While 3D models were maintained for 10 days and processed for calcium imaging and immunostaining, 2D cell cultures were maintained for a week and used for gene expression analysis and immunostaining. Cells that had been cultured in 2D cultures or 3D models underwent immunofluorescence. Beta-amyloid (A) plaque-like formations were measured for relative size and quantity.

The key findings of this study were:

1. This screening revealed that resveratrol and green tea catechins have potent anti-plaque properties, functional neuroprotective advantages, and little neurotoxicity, supporting further research into these compounds as AD preventives and treatments.

2. Citicoline and metformin, two further options, decreased plaque formation and had low toxicity, but they provided little protection against virus-induced alterations in neural signaling.

In conclusion, according to the study, resveratrol and green tea catechins are attractive candidates because of their anti-plaque effects, functional neuroprotective qualities against AD, and low toxicity. Although treatments with citicoline and metformin showed plaque reduction and low toxicity, these drugs were not effective in protecting against HSV-induced changes in neuronal transmission. Overall, using 2D cell cultures and 3D human brain tissue models, the work provided a straightforward platform for the quick screening and characterization of drugs against AD.

Reference:

Silveira, I. A., Mullis, A. S., Cairns, D. M., Shevzov-Zebrun, A., Whalen, J., Galuppo, A., Walsh, K. G., & Kaplan, D. L. (2022). Screening neuroprotective compounds in herpes-induced Alzheimer's disease cell and 3D tissue models. In Free Radical Biology and Medicine (Vol. 186, pp. 76–92). Elsevier BV. https://doi.org/10.1016/j.freeradbiomed.2022.05.002