Scientists have identified a potential new target for treating Alzheimer's disease that works by restoring the brain's own "self-cleanup" process.
The target is already used in preexisting Parkinson's drugs and demonstrated partial reversal of cognitive deficits in aged study mice.
Alzheimer's affects roughly 5.8 million Americans, according to the Centers for Disease Control and Prevention. The progressive disease is the most common form of dementia and is associated with memory loss and cognitive decline in regions of the brain involved in thought, memory and language.
There is no known cure for Alzheimer's, although scientists believe that it is caused by the abnormal buildup of proteins in and around the brain cells. One of the major components of these abnormal aggregates is a protein called amyloid beta.
Amyloid beta is produced when proteins in the brain misfold and clump together. These clumps initiate a variety of damaging chemical reactions around our brain cells that damage and eventually destroy them.
Normally, our brain's cellular cleanup crew, which includes an enzyme called neprilysin, clears away any excess proteins and cellular debris.
"Neprilysin has been identified as the most potent amyloid beta degrading enzyme in the brain," Naoto Watamura, a research fellow at the UK Dementia Research Institute at University College London and the RIKEN Brain Sciences Center in Japan, told Newsweek.
However, preliminary evidence has shown that, as we age, levels of neprilysin in the brain tend to decline. Studies have also shown that genetically engineered mice that do not produce this enzyme develop very high levels of toxic amyloid beta protein clumps.
But while these findings suggest that neprilysin is a key player in the onset of neurodegenerative disease, methods to target and upregulate its activity have remained elusive—until now.
In a new study published in the journal Science Signaling, Watamura and colleagues from the RIKEN Brain Sciences Center screened a range of different candidate compounds and found one molecule that was able to upregulate the activity of this essential enzyme: dopamine.
You might have heard dopamine being referred to as the "pleasure hormone" due to its role in the brain's reward center. But the neurotransmitter has many other roles in our brains too. "Dopamine regulates emotion, movement, and motivation," Watamura said.
And, according to these findings, dopamine may also play a role in staving off cognitive decline.
By studying mice, the team found that the release of dopamine was associated with an increase in neprilysin abundance and subsequent degradation of amyloid beta buildups in the "personality center" of the brain, also known as our prefrontal cortex.
This isn't entirely surprising as dopamine (or a lack of it) has already been shown to play an important role in the development of Parkinson's disease. Indeed, the majority of existing Parkinson's medications work by increasing dopamine levels in the brain or simulating its effects.
One of the main drugs used to treat Parkinson's is levodopa, a dopamine precursor synthesized into the neurotransmitter in the brain. By giving these approved Parkinson's drugs to aged mice and mice engineered to model the symptoms of Alzheimer's, Watamura and colleagues found similar improvements in amyloid beta levels in the brain and partial reversal of cognitive deficits.
"I was [surprised] because dopamine, which is likely to be the central role of Parkinson's disease, could have the potential to treat the aspect of Alzheimer's disease pathology," Watamura said.
Their findings may also offer insights into the established associations between dementia and mental health disorders related to low levels of dopamine.
Further research is needed to confirm these findings in humans, but the researchers are hopeful that their results may offer new targets for the treatment of Alzheimer's disease.
"Based on these findings, we aim to investigate a further downstream mechanism by which dopamine regulates neprilysin and develop the fundamental therapy for Alzheimer's disease," Watamura said.
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