The formation of these plaques around neurons is one of the first signs of the disease, which often begins decades before the first behavioral symptoms appear. These plaques are made up of pieces of the beta-amyloid peptide that build up over time. However, levels of the enzyme neprilysin are inversely associated with the importance of beta-amyloid plaques and cognitive decline.
Produce more neprilysin
If genetic manipulation to produce neprilysin is possible for experimental purposes, to treat humans, it is a question of finding drugs that induce this same effect. However, neprilysin tablets or injections are not possible in humans, because the enzyme cannot penetrate the brain through the bloodstream.
The study So first consisted of examining numerous molecules to determine which ones can naturally regulate neprilysin in the right regions of the brain. Previous research has prompted scientists to focus on hormones produced by the hypothalamus. This research led to dopamine, which they show increases, in vitro, the levels of neprilysin in brain cell cultures and reduces their levels of beta-amyloid.
L-DOPA boosts neprilysin which reduces harmful beta-amyloid plaques
A preclinical study, subsequently carried out on the mouse model of Alzheimer’s, reveals that the insertion of tailor-made receptors in the mice’s dopamine-producing neurons, which makes it possible to continuously activate these neurons, leads to an increase in neprilysin and a decreased levels of beta-amyloid.
L-DOPAa dopamine precursor molecule often used to treat Parkinson’s disease, similarly led to an increase in neprilysin and a decrease in beta-amyloid plaques in the brains of these mouse models treated for 3 months. If the result is there, the researchers do not know how to explain at this stage the underlying mechanism of the drug.
“We show that L-DOPA can help reduce harmful beta-amyloid plaques and improve memory in a model of Alzheimer’s disease”summarizes the lead author, researcher Watamura Naoto. Researchers hope for similar results in future clinical trials (in humans), which could lead to new, more effective options for treating or slowing the progression of the disease.
« But L-DOPA treatment is known to have serious side effects in Parkinson’s patients. Therefore, our next step will be to look at how dopamine regulates neprilysin in the brain, which should give rise to a new preventive or even curative approach to Alzheimer’s disease.
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