Skip to comments.Combination therapy reduces toxic aggregates in Parkinson's disease (diltiazem (a calcium channel blocker))
Posted on 11/30/2021 2:10:46 PM PST by ConservativeMind
A new combination of drugs could fix the broken lysosomal enzyme pathway in Parkinson's disease-afflicted brain cells.
Improving transport of these enzymes can boost lysosomal function, aiding the cellular organelle in breaking down harmful protein aggregates that are a primary cause of symptoms in Parkinson's disease (PD), according to Joseph Mazzulli, Ph.D.
"We think moving forward, these combination therapies would be very effective," Mazzulli said.
A defining characteristic of PD is the accumulation of misfolded alpha-synuclein proteins in the brain. These proteins aggregate and form clumps which are linked to a variety of harmful effects including oxidative stress, inflammation and mitochondrial dysfunction.
The ER is where proteins are initially synthesized and folded, including important enzymes required for proper lysosome function. Here, alpha-synuclein binds to the ER and inhibits folding, leading to buildup of malformed proteins that are unable to exit the ER to their next organelle destination.
Using patient-derived midbrain neurons modeling the disease, Mazzulli and his collaborators found that an FDA-approved drug—diltiazem—can restore proper folding and prevent clumping of enzymes.
"It actually enhances activity of what we call 'folding chaperones' and dissolves the aggregates into functional components, so they can leave the ER," Mazzulli said.
From the ER, these enzymes travel to the Golgi apparatus, which packages and ships materials all over the cell. Here too, alpha-synuclein interferes with function, reducing the amount of proteins or enzymes that can pass through the Golgi. However, another drug—a farnesyl-transferase inhibitor—has been shown to restore proper Golgi activity.
"This compound actually opens up more lanes on the highway through the Golgi," Mazzulli said.
Applying both drugs to patient-derived PD neurons restored lysosome function and allowed the organelle to dispose of alpha-synuclein, a result that could potentially reduce symptoms in patients.
(Excerpt) Read more at medicalxpress.com ...
Thanks for posting!
started searching “gingerol” using the gibiru.com search engine.
more ginger chemistry
Fresh raw ginger root consists of various chemical compounds, including zingiberene, which makes up about 30% of the essential oil found in the root. It also consists of other compounds such as ß-sesquiphelandrene and ar-curucumene but the pungency is down to the presence of compounds known as gingerols. Chemically, gingerol is related to capsaicin, the compound that makes chillies so spicy, and piperine, a compound present in black pepper.
Interestingly, some gingerol is altered when ginger is cooked and can even transform into different a different compound. When ginger is heated, gingerol changes and becomes zingerone, due to a reverse aldol reaction. This process softens the pungent taste found in fresh ginger and produces a spicy yet sweet aroma, just like the ginger we can taste in gingerbread.
However, when ginger is dried or slightly heated, gingerol goes through a dehydration process, which forms shogaols – compounds about twice as spicy as gingerol! This explains why when dry, ginger has a much stronger pungency to it than fresh ginger.
It may be more popular over Christmas, but with so many ways to cook and serve ginger, there really isn’t a right or wrong time to enjoy the spice is there?
Thank you for that. I didn’t understand why forms of ginger could taste so different, but it makes sense, now.
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