Artificial enzyme could slow Parkinson's by targeting protein clumps
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.”
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 nanoenzymes work when injected directly into the brain,” says Mao. “Now, we’d like to see if the nanoenzymes 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