New Drug Targets to Help Fight Alzheimer's Disease Identified

Two classes of drug compounds that could help combat Alzheimer's disease have been unveiled by scientists.

Their research suggests that these compounds target the disease-causing peptides with high precision and with minimal side-effects.

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At the same time, the scientists offer a molecular explanation for early-onset hereditary forms of Alzheimer's, which can strike as early as thirty years of age.

The conclusions of their research are very encouraging regarding the future of therapeutic means that could keep Alzheimer's disease in check.

Alzheimer's disease is characterized by an aggregation of small biological molecules known as amyloid peptides.

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We all produce these molecules; they play an essential antioxidant role.

But in people with Alzheimer's disease, these peptides aggregate in the brain into toxic plaques - called "amyloid plaques" - that destroy the surrounding neurons.

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The process starts with a long protein, "APP", which is located across the neuron's membrane.

This protein is cut into several pieces by an enzyme, much like a ribbon is cut by scissors.

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The initial cut generates a smaller intracellular protein that plays a useful role in the neuron. Another cut releases the rest of APP outside the cell - this part is the amyloid peptide.

For reasons not yet well understood, APP protein can be cut in several different places, producing amyloid peptides that are of varying lengths.

Only the longer forms of the amyloid peptide carry the risk of aggregating into plaques, and people with Alzheimer's disease produce an abnormally high number of these.

The two next-generation classes of compound that are currently in clinical trials target an enzyme that cuts APP, known as gamma secretase.

Until now, our understanding of the mechanism involved has been lacking.

But with this work, the EPFL researchers were able to shed some more light on it by determining how the drug compounds affect gamma secretase and its cutting activity.

The study is published in the journal Nature Communications.

Source-ANI