Johns Hopkins scientists have created artificial enzymes that may slow the progression of Parkinson's
Neurodegenerative diseases like Parkinson’s
are characterized by clumps of misfolded proteins accumulating and killing
brain cells. Now, researchers at Johns Hopkins have developed an artificial
enzyme that may stop these clumps from spreading, providing a new potential
treatment for Parkinson’s.
Alpha-synuclein is an abundant protein in
the brain, but over time it can misfold and form clumps called Lewy bodies. If
these clumps accumulate they can kill off neurons, resulting in problems with
motor control, cognition and behavior associated with Parkinson’s disease.
In the new study, the Johns Hopkins
researchers developed an artificial enzyme that could stop these Lewy bodies
from spreading. The “nanozymes” are alloys of platinum and copper, designed to
mimic catalase and superoxide dismutase, two natural enzymes in the body that
target reactive oxygen species.
“Oxidative stress caused by reactive oxygen species is inescapable, and increases with age due to mechanistic slowdowns in processes such as protein degradation,” says Xiaobo Mao, senior author of the study. “This indicates the importance of antioxidants, because in Parkinson’s disease, roaming reactive oxygen species promote the spread of misfolded alpha-synuclein, leading to worse symptoms.”
A protein clump called a Lewy body (center), along with a map (inset) of where in the brain the scan was taken
The researchers tested the nanozyme by
injecting preformed clumps of alpha-synuclein proteins into the brains of mice,
then following up with injections of the new artificial enzymes. They found
that the nanozyme scavenged the reactive oxygen species, significantly
inhibiting transmission of the Lewy bodies between neurons. That in turn
reduced cell death and other pathological symptoms linked to Parkinson’s and
other neurodegenerative diseases.
The next steps, the team says, are to
investigate whether the treatment could be used to target the gut – a potential
starting point for the disease according to what’s known as Braak’s hypothesis.
The idea is somewhat divisive in the scientific community, but there’s a growing
body of evidence supporting it.
“We know that the Nano enzymes work when
injected directly into the brain,” says Mao. “Now, we’d like to see if the Nano enzymes can block the disease progression induced by pathogenic alpha-synuclein
traveling from the gut, across the blood-brain barrier and into the brain.”
The research was published in the
journal Nano Today
Source: Johns Hopkins Medicine
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