Researchers have discovered how a molecule found in green tea breaks apart tangles of the protein tau, a hallmark of Alzheimer’s disease. Based on this finding, the team identified other molecules that can also untangle tau and may be better drug candidates than the green tea molecule. Results from the NIA-funded study, published in Nature Communications, suggest that this approach may one day provide an effective strategy for treating Alzheimer’s.
In Alzheimer’s, tau abnormally sticks together in fibrous tangles that spread between brain cells, leading to cell death. The molecule epigallocatechin gallate (EGCG) — the one found in green tea — is known to untangle these tau fibers. However, EGCG is not on its own an effective Alzheimer’s treatment because it cannot easily penetrate the brain and binds to many proteins other than tau, weakening its effect. Therefore, researchers wanted to find molecules that replicate the effects of EGCG but have better drug properties for treating Alzheimer’s.
New electrical method triggers and analyzes dynamics of brain protein that underlie many neurodegenerative diseases
Scientists are not yet clear on how the tau protein changes from a benign protein essential for normal function in our brains into the toxic neurofibrillary tangles that are a signature of Alzheimer’s and other neurodegenerative diseases.
But a new method developed by researchers at UC Santa Barbara gives the ability to control and follow in real time the process by which it happens. The technique employs a novel use of low voltage electricity as a surrogate for the natural signals that trigger the protein to fold and assemble, both for its normal function in the brain and in the runaway process leading to often fatal disease.
“This method provides scientists a new means to trigger and simultaneously observe the dynamic changes in the protein as it transitions from good to bad,” said Daniel E. Morse, Distinguished Professor Emeritus of Biochemistry and Molecular Genetics, and senior author of a paper that appears in the Journal of Biological Chemistry.
“The method should be widely useful to identify molecules and conditions that direct different trajectories of assembly in a number of different but related amyloid diseases,” stated Eloise Masqulier, lead author of the interdisciplinary team of students, researchers and faculty from molecular biology, chemistry and engineering including Esther Taxon, Sheng-Ping Liang, Yahya Al Sabeh, Lior Sepunaru and Michael J. Gordon.