Molecule Found in Green Tea Can Break Up Alzheimer’s-Causing Protein Tangles, BrightFocus Researcher Finds

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Using a molecule found in green tea, a team of biochemists have identified new molecules that can destroy protein tangles in the brain linked to Alzheimer’s and related brain diseases.

Alzheimer’s Disease Research grantee Paul Seidler, PhD, was the lead author of the study published in Nature Communications. Dr. Seidler received a grant from Alzheimer’s Disease Research, a program of BrightFocus Foundation, to study how tau is structurally assembled to prevent dysfunctional aggregation of the protein.

The researchers’ goal was to identify molecules that were better than the green tea molecule EGCG at breaking up tau fibers, which are long, multilayered filaments that form tangles that attack neurons, causing them to die. “If we could break up these fibers, we may be able to stop death of neurons,” said study author David Eisenberg, a UCLA professor of chemistry and biochemistry whose lab led the new research.

Tau is an amyloid protein that, along with amyloid beta, is associated with Alzheimer’s. Many scientists think removing or destroying tau fibers can halt the progression of dementia. Additionally, they believe that tau’s influence over Alzheimer’s disease may be equal to or even greater than that of amyloid beta as it is associated with the rapid progression of Alzheimer’s disease.

Unfortunately, although it has long been known that EGCG can break up tau fibers, EGCG is not an effective dementia treatment as it does not enter cells or the brain easily. But knowing that EGCG could disrupt tau helped the scientists identify other molecules with more promise. First, they identified specific locations, called pharmacophores, on the tau fiber to which EGCG molecules attached. Then they ran computer simulations on a library of 60,000 brain and nervous system-friendly small molecules with the potential to bind to the same sites. They found several hundred molecules that were 25 atoms or less in size, all with the potential to bind even better to the tau fiber pharmacophores.

From the computational screening, the team identified about a half dozen molecules that broke up the tau fibers. Of these compounds, molecules CNS-11 and CNS-17 also stopped the fibers from spreading from cell to cell. The researchers think these molecules are candidates for drugs that could be developed to treat Alzheimer’s and related diseases.

“For cancer and many metabolic diseases, knowing the structure of the disease-causing protein has led to effective drugs that halt the disease-causing action,” Dr. Eisenberg said. “But it’s only recently that scientists learned the structures of tau tangles. We’ve now identified small molecules that break up these fibers. The bottom line is, we’ve put Alzheimer’s disease and amyloid diseases in general on the same basis as cancer, namely, that structure can be used to find drugs.”

Dr. Eisenberg said that the molecules the team identified are not yet drugs, but “by studying variations of this, which we are doing, we may go from this lead into something that would be a really good drug.”