University of Pennsylvania School of Medicine scientists have identified a new class of compounds that can help develop Alzheimer's drugs.
The new class of molecules is capable of blocking the formation of specific protein clumps that are believed to contribute to the dementia of Alzheimer's disease (AD) patients.
By assaying close to 300,000 compounds, they have identified drug-like inhibitors of AD tau protein clumping.
During the study, the researchers looked for small molecules that prevent the formation of the tau protein fibrils.
These fibrils, a hallmark pathological feature of AD, have been a holy grail for investigators hoping to better treat AD and related neurodegenerative diseases.
Tau fibrils accumulate as insoluble deposits in brain nerve cells of patients with a host of debilitating neurodegenerative diseases, the most prevalent of which is AD.
Since these tau aggregates are found in several neurodegenerative disorders and are thought to contribute to disease pathology, it is hoped that drugs that prevent these deposits might prove to be effective therapeutic agents for AD and related disorders.
The team found a total of 285 compounds that were of potential interest, and of these they focused on a specific chemical series called ATPZs that effectively block fibril formation.
The ATPZs fit most of the criteria for potential drug candidacy such as proper size, desirable chemical properties, specificity for the tau protein, and a predicted likelihood of crossing the blood-brain barrier.
"This led us to further explore this unique chemical series," said Dr Kurt R. Brunden, Director of Drug Discovery at Penn's Centre for Neurodegenerative Disease Research (CNDR).
"While we are excited about the discovery of this new series of tau fibril inhibitors, we are still a long ways from turning these early lead compounds into drugs.
"However, we believe that certain of our ATPZ compounds will be very useful in allowing us to gain a better understanding of the consequences of inhibiting tau fibril formation in transgenic mouse models of Alzheimer's disease," he added.
The study appears in the journal Biochemistry.