Green tea catechins and resveratrol display neuroprotective properties in Alzheimer's models GreenTea Resveratrol Tea Alzheimers Neurology TuftsUniversity
Alzheimer’s disease, the sixth leading cause of death in the United States , is a progressive neurodegenerative condition and the common cause of dementia in older adults. Increasing evidence suggests that pathogens trigger the amyloid cascade, tau protein hyperphosphorylation, and neuroinflammation in some patients. Specifically, herpes simplex virus type 1 is implicated as an etiologic agent in sporadic AD .
The study and findings In the present study, researchers screened for neuroprotective compounds against AD. Human-induced neural stem cells were generated by direct reprogramming using human foreskin fibroblasts. These cells were infected with HSV-1 at a multiplicity of infection of 0.0001. 3D human cortical brain tissue models were generated. Experimental compounds were added concurrently with viral inoculums.
The primary 2D screen was performed using the entire library of 21 compounds to test the formation of Aβ plaque-like formations, mRNA transcripts of AD mediators (amyloid precursor protein [APP], presenilin 1 [PSEN1], and cell morphology. The lead candidates from the 2D screen were advanced to testing in 3D tissue models for plaque-like formations, dendritic network integrity, and calcium imaging.
Curcumin treatment decreased plaque count and size in HSV-1-infected 2D cultures. Moreover, curcumin treatment caused significant cell death at 100 μM. 10 μM curcumin treatment restored APP and PSEN1 expression levels to non-infected levels. Of note, curcumin treatment of 3D tissues caused significant cell death and thus was not further studied.
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