What does it mean to be closer to
finding the cure for diseases that no one has truly been able to
understand? Alzheimer’s disease (AD) and
other non-inheritable dementias may not all have one specific cause or origin,
yet they may all have certain pathways in common. Many researchers have dedicated years of
extensive research in an attempt to map out the neural circuitry of the
brain. Contrary to popular opinion,
there is so little we really know when it comes to how the brain functions in
relation to many diseases.
In correspondence to the same
mission, much light has been recently shed on the study of neuroprotection in
the brain and the underlying mechanisms behind the regulation of specific
proteins. Dr. Michael Collins came to Loyola University Chicago on October 13,
2015 to speak about his research on ethanol preconditioning and brain
neuroprotective signaling. Moderate
ethanol preconditioning (MEP) was applied to cultures of rat brains in order to
study possible mechanisms that can provide neuroprotection to the brain. About 20 to 30mM of ethanol seemed to cause
neuroprotection by preventing the effects of neurotoxic proteins.
The first part of this study focused
on trying to understand the mechanisms that would lead to a neuroprotective
state in the brain. Specifically, MEP
was seen to cause changes in NMDA receptor activity. Any major increase or decrease in activity of
this receptor was also seen to increase activity in PKC. Upstream PKC activity corresponded to increased
activity of another tyrosine phosphorylating enzyme, FAK. Finally, this leads to increased activity in
the antioxidant protein, peroxiredoxin 2 (Prx2), which corresponds to a
neuroprotective state of the brain.
The second part of this study focused
on taking this new information a step further and charting into the
unknown. Previous studies were seen to
show a similar mechanism in terms of trans-reservatrol, the natural compound
found in red wine. Trans-reservatrol
also increased activity of the Prx2 enzyme causing protection from beta
amyloids. It was found that 5 ɥM of this
compound lead to neuroprotection. Now,
the big question was if one could synergize the preconditioning modalities
combinatorially? Combining 10 mM of
ethanol and 5 ɥM reservatrol actually decreased death of neurons down to 10
percent!
It turns out that Dr. Collin’s study
was not the only one interested in the neuroprotection made possible by
trans-reservatrol. In fact, just last
year the Journal of Alzheimer’s Disease
published a study that analyzed the protein, Sirtuin 1. The activity of this protein increases with
added amounts of reservatrol. Dr.
Porquet and researchers at the University of Barcelona fed a dietary
supplementation amount of reservatrol for 10 months to a group of mice that
were modified to develop Alzheimer’s disease.
According to Mercè Pallàs, researcher from the Research Group on Aging
and Neurodegeneration of UB and the Centre for Networked Biomedical Research on
Neurodegenerative Diseases (CIBERNED), “Results showed that reservatrol
ameliorated short-term memory and stopped the accumulation of senile plaques
and the development of the tau protein, the two most important characteristics
of the disease.” Analysis of the Sirtuin
pathway in terms of reservatrol emphasizes the importance reservatrol has on
neuroprotection for the brain. This
study in combination with Dr. Collin’s research shows that understanding the
different mechanisms and pathways which influence a single response is much
more complex than originally predicted.
It also opens up uncharted territory in terms of explanations for
different non-inheritable mental illnesses.
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