Will dipeptides help with Alzheimer's disease?
Alzheimer's disease is the main cause of senile dementia. In the world, about 15 million people suffer from this neurodegenerative disease, which medicine could not fight until now.
Long before the manifestation of clinical symptoms in the brains of patients with Alzheimer's syndrome, amyloid plaques appear – deposits of improperly organized amyloid beta-peptides. Previously, it was suggested that these plaques cause degeneration of nerve cells, but recent studies indicate that the main cause of memory loss is smaller and soluble aggregates of amyloid-forming peptides. These amyloid oligomers turn out to be very toxic to nerve cells. A new approach to the treatment of Alzheimer's syndrome, proposed by Ehud Gazit from Tel Aviv University, aims to block the formation of these toxic oligomers.
When designing the molecule, the need for the content of an aromatic amino acid residue and a destroyer of beta-sheets of protein was taken into account. The aromatic fragment plays a key role in the aggregation of amyloid-forming peptides, since the drug must bind to the aromatic core of the beta-amyloid peptide due to the aromatic fragment. During aggregation of amyloid plaques, proteins take the form of beta folds, so the drug should prevent proteins from forming this type of secondary structure. Also, the drug molecule should be small so that it can be absorbed by the digestive tract after oral administration. The dipeptide developed in the Gazita group satisfies all these requirements: it is formed by non-proteinogenic amino acids (not part of ordinary proteins); alpha-aminoisobutanoic acid acts as a destroyer of the beta-folded structure; the second acid, D-tryptophan, contains an indole fragment binding to aromatic molecules. D-tryptophan stabilizes the dipeptide, since D-amino acids are processed more slowly in the body than their natural L-analogues.
Researchers from Israel report that the dipeptide they developed increases the cognitive ability of mice with an analog of human Alzheimer's disease and reduces the number of amyloid plaques in their brains. The article by Anat Frydman-Marom et al. Cognitive-Performance Recovery of Alzheimer's Disease Model Mice by Modulation of Early Soluble Amyloidal Assemblies is published in the journal Angewandte Chemie.
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