Novel Parkinson's disease treatment based on artificial enzymes

Parkinson's disease is the second most common neurodegenerative disease in the world, after Alzheimer's disease
.

The etiology of the disease is unknown, which also means that there is currently no effective treatment
.

In recent years, researchers have tried a variety of treatments to better understand the brain, ranging from hydrogels to personalized brain cell transplants, but have so far failed
.

Scientists at the Sixth People's Hospital Affiliated to Shanghai Jiaotong University recently researched a new way to treat the disease
.

Researchers have designed artificial enzymes (namely nanozymes) based on nanomaterials to treat Parkinson's disease.
The related results were published in the journal Advanced Materials
.

Prussian blue enzyme (PBzyme), a Prussian blue-based artificial nanozyme, was applied to mouse models and found to be effective in alleviating neurodegenerative-related inflammation
.

The nanozyme also protects neurons and microglia, the main immune cells of the central nervous system, from the drug MPTP, which has long been thought to induce the rapid onset of Parkinson's disease
.

Schematic of Prussian blue enzyme as an inhibitor of pyroptosis, an inflammatory cell death, in the treatment of Parkinson's disease.
Prussian blue is currently approved by the U.
S.
Food and Drug Administration as an antidote for the treatment of thallium and other radioactive elements poisoning
.

In addition to this, Prussian blue enzyme is also able to scavenge reactive oxygen species such as hydroxyl radicals and peroxides
.

These molecules, in turn, promote the development of an inflammatory response, particularly on the protein NLRP3
.

NLRP3 can trigger an inflammatory response in cells under oxidative stress caused by reactive oxygen species, which is thought to play a key role in the development of Parkinson's disease
.

In this article, the team hopes to use Prussian blue enzyme to cut this immune response at the source, and obtain some positive preliminary results
.

As shown, after cells were treated with MPTP, Prussian blue enzyme scavenged the reactive oxygen species produced by the cells, thereby disrupting the NLRP3 inflammatory response chain that can lead to neuronal death
.

In animal experiments, MPTP-induced Parkinson's disease mice were injected with Prussian blue enzyme 10 days after the onset of the disease, and it was found that the deterioration of their motor function was significantly alleviated and improved
.

However, there was no significant difference in motor function before and after the injection of Prussian blue enzyme in the control group (non-Parkinson's disease group), suggesting that Prussian blue enzyme has no adverse effect on the nervous system
.

Follow-up studies also showed that most Prussian blue enzymes in the body can be metabolized in about 30 days
.

While no apparent adverse effects were found in mice, a follow-up study is needed to look at the long-term potential toxicity of Prussian blue enzyme before the therapy enters Phase 1 human trials
.

Regardless, as we learn more about the underlying etiologies of Parkinson's disease and other neurodegenerative diseases, Prussian blue nanozymes may become effective tools for long-term treatment and care of such diseases in the future
.

WILEY References: Xinxin Ma et al.
, Prussian Blue Nanozyme as a Pyroptosis Inhibitor Alleviates Neurodegeneration, Advanced Materials (2022).
DOI: 10.
1002/adma.
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