Deans' stroke musings: Parkinson’s Progression Halted by Inhibiting Enzyme

Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.

Wednesday, November 15, 2023

Parkinson’s Progression Halted by Inhibiting Enzyme

With your risk of Parkinsons post stroke, your competent doctor should be ready to apply this or at least get human research going. Or don't you have a competent doctor?

Parkinson’s Disease May Have Link to Stroke March 2017

Parkinson’s Progression Halted by Inhibiting Enzyme

Summary: Researchers discovered that inhibiting a specific enzyme, USP30, in a mouse model protects dopamine-producing neurons, which are typically lost as the disease progresses.

This groundbreaking finding suggests a new therapeutic avenue that could slow or even prevent Parkinson’s progression.

The study involved both genetic and pharmacological methods to demonstrate the protective effects of USP30 inhibition on neuronal health and disease symptoms.

Key Facts:

The study showed that inhibiting the USP30 enzyme protected dopamine-producing neurons in a Parkinson’s mouse model.
Researchers used both genetic ‘knockout’ models and a proprietary molecule to block USP30, leading to increased clearance of damaged mitochondria.
These findings offer new hope for developing treatments that could potentially modify the course of Parkinson’s disease.

Source: BIDMC

In a new study, investigators at Beth Israel Deaconess Medical Center (BIDMC) have shed new light on key cellular processes involved in the progression of Parkinson’s disease (PD).

The research is published in the journal Nature Communications.

Affecting around 10 million people worldwide, Parkinson’s disease is a neurodegenerative disorder caused by the progressive loss of the group of brain cells responsible for producing dopamine, a neurotransmitter that plays a critical role in regulating movement and coordination.

This shows a neuron. — “The two experimental strategies together are much more convincing than either alone,” said Simon, who is also a professor of neurology at Harvard Medical School. Credit: Neuroscience News

As these neurons degenerate and dopamine levels decrease, individuals with Parkinson’s disease experience a wide range of symptoms, including tremors, stiffness and difficulties with balance and coordination.

Researchers in the lab of senior author David K. Simon, MD, Ph.D., director of the Parkinson’s Disease & Movement Disorders Center at BIDMC, in collaboration with colleagues at the University of Cambridge and Mission Therapeutics, performed complementary experiments showing that inhibiting a specific enzyme in a mouse model protects the dopamine-producing neurons that are normally lost as PD progresses, effectively halting the progression of the disease.

The findings open the door to the development of novel therapeutics targeting the enzyme that may slow or prevent the progression of Parkinson’s disease in people—a major unmet need.

“Our lab is focused on working out the origins of Parkinson’s disease and it is our hope that—one day—we will be able to slow down or even prevent disease progression in patients,” said first author Tracy-Shi Zhang Fang, Ph.D., an instructor in Simon’s lab. “The current study’s findings pave the way toward that future.”

Evidence suggests the dopamine-producing cells die off in Parkinson’s disease because something has gone awry with the clearance of the cells’ old and dysfunctional mitochondria—organelles that are the source of cells’ energy, sometimes called the powerhouse of the cell.

Simon and colleagues focused on an enzyme called USP30 which plays a role in this process. In a mouse model engineered to lack the gene that produces the enzyme—known as a “knockout model” because one specific gene has been deleted for the purposes of experimentation—the researchers observed that the loss of USP30 protected against the development of Parkinson’s-like motor symptoms, increased clearance of damaged mitochondria in neurons, and protected against the loss of dopamine-producing neurons.

In a second set of experiments, the team validated the knockout studies using a proprietary molecule developed by Mission Therapeutics to block the enzyme’s action in the dopamine-producing neurons.

As in the knockout mice, inhibiting the enzyme’s action increased clearance of dysfunctional mitochondria and protected dopamine-producing neurons.

“The two experimental strategies together are much more convincing than either alone,” said Simon, who is also a professor of neurology at Harvard Medical School.

“Together, our very significant findings support the idea that reducing USP30 warrants further testing for its potentially disease-modifying effects in PD.”