How a small molecule in green tea and other, newly discovered similar compounds break amyloid tangles that cause Alzheimer’s

Drink more green tea! So healthy and delicious! Tea leave reading becomes a whole new meaning! 😊

"... In a paper ... biochemists describe how EGCG snaps tau fibers layer by layer. They also show how they discovered other molecules likely to work the same way that would make better potential candidates for drugs than EGCG, which can’t easily penetrate the brain. The finding opens up new possibilities for fighting Alzheimer’s, Parkinson’s and related diseases by developing drugs that target the structure of tau fibers and other amyloid fibrils. ..."

From the abstract:

"Alzheimer’s disease (AD) is the consequence of neuronal death and brain atrophy associated with the aggregation of protein tau into fibrils. ... The small molecule EGCG, abundant in green tea, has long been known to disaggregate tau and other amyloid fibrils, but EGCG has poor drug-like properties, failing to fully penetrate the brain. Here we have cryogenically trapped an intermediate of brain-extracted tau fibrils on the kinetic pathway to EGCG-induced disaggregation and have determined its cryoEM structure. The structure reveals that EGCG molecules stack in polar clefts between the paired helical protofilaments that pathologically define AD. Treating the EGCG binding position as a pharmacophore, we computationally screened thousands of drug-like compounds for compatibility for the pharmacophore, discovering several that experimentally disaggregate brain-derived tau fibrils in vitro. This work suggests the potential of structure-based, small-molecule drug discovery for amyloid diseases."

Newly identified small molecules break amyloid tangles that cause Alzheimer’s | UCLA A molecule found in green tea helped UCLA biochemists discover several molecules that can destroy tau fibers

Structure-based discovery of small molecules that disaggregate Alzheimer’s disease tissue derived tau fibrils in vitro (open access)

Fig. 1: CryoEM structure of AD-tau PHF in complex with EGCG