Zinc may enhance the protective role of a protein

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Consuming zinc-rich foods may help boost the protective role of a transport protein against Parkinson’s disease. Helen Rushbrook/Stocksy
  • Experts believe that several factors contribute to the development of Parkinson’s disease. Some studies suggest that one factor may be the formation of Lewy bodies in the brain, created by clumps of a protein called alpha-synuclein.
  • Previous research has shown that zinc can increase alpha-synuclein buildup. Yet the mechanisms behind this process are not well understood.
  • A new study conducted uunder biologically relevant conditions found that zinc may have an unexpected role in preventing alpha-synuclein buildup by enhancing a transport protein called albumin to inhibit clustering.
  • The research highlights the need to study biological pathways under conditions that mimic natural organisms.

Parkinson’s disease is a condition that affects the nervous system and causes symptoms such as changes in movement, coordination and cognitive function.

One of the key factors in the development of Parkinson’s disease is the accumulation of a protein called alpha-synuclein (AS). AS congregation leads to the formation of Lewy bodies in the brain, potentially leading to neuron dysfunction.

Additionally, a 2019 study suggests that human serum albumin (HSA) – an abundant transport protein in the body – may play a role in inhibiting SA accumulation.

Yet according to another study published in 2019, the disordered physiological processes associated with the development of neurodegenerative diseases may also involve metals, including zinc, copper and iron.

This association between neurodegenerative conditions and metals – particularly zinc – has reappeared in recent research by scientists in China. The researchers suggest that zinc ions (Zn2+) play an important role in the accumulation of SA.

Additionally, the research underscores the need to conduct biological pathway experiments under conditions that closely mimic natural organisms.

The study appears in the International Journal of Biological Macromolecules.

Due to the previously revealed associations between zinc, HSA, AS and Parkinson’s disease, scientists sought to investigate how zinc ions affect the binding actions of AS.

Samah Al-Harthi, Ph.D. student and co-author of the study, says Medical News Today:

“The protein alpha-synuclein (AS) is thought to play an important role in the development of Parkinson’s disease (PD) and contributes to the pathogenesis of PD in several ways. The toxic forms created and co-created by the oligomerization and aggregation of alpha-synuclein can cause neuronal dysfunction. Thus, the presence of the healthy and functional state of the most abundant protein in humans, human serum albumin (HSA), also present in cerebrospinal fluid (CSF), may open pathways as preventive treatment.

The research team used a specially designed nuclear magnetic resonance (NMR) spectrometry imaging system to conduct the study. This innovative imaging technique allowed the team to monitor proteins, including AS, under physiological conditions close to those encountered in a natural organism.

Under non-physiological and physiological conditions, scientists have studied the interaction of AS with zinc ions, AS with HSA, and the three components combined.

After compiling the data, the researchers found that the accumulation and binding of AS occurred more rapidly with increased concentrations of zinc ions.

However, adding HSA along with zinc ions under physiological conditions had the opposite effect, essentially slowing AS aggregation.

“Zinc ions (Zn2+) have been shown to significantly accelerate AS amyloid fibril formation in vitro in a simple two-component system,” Al-Harthi explained. “However, adding HSA and Zn2+ and maintaining physiological conditions of ionic strength and temperature had the opposite effect, slowing AS aggregation.”

“Based on our systematic studies, we suggest that Zn2+ enhances the chaperone abilities of HSA,” she said. “This is a key finding, as it highlights that zinc ions under physiological conditions of a crowded and complex cellular context enhance the protective role, hence the proper functioning of HSA.”

Al-Harthi added that HSA, synuclein and zinc ions coexist under physiological conditions in blood and brain fluids.

“Our studies underscore that these medically relevant biomolecules cannot be studied in isolation to make medically relevant discoveries that may be of any future therapeutic use,” she said.

After reviewing the research, Dr. Christopher J. Barnum, director of neuroscience at INmune Bio in Boca Raton, FL, said DTM:

“The therapeutic impact of this study is based on the hypothesis that alpha-synuclein causes Parkinson’s disease. There is no equivocal evidence that this is true. We have already seen this in Alzheimer’s disease with amyloid. Hundreds of studies have conclusively demonstrated that amyloid therapies are not the panacea once believed to be.

Dr Barnum added that despite previous evidence, the field of Parkinson’s disease is “increasingly focused on alpha-synuclein – in its models, biomarkers and preferred therapies”.

“Maybe this time it won’t take a hundred failed clinical trials to adopt other mechanisms,” he said.

Al-Harthi said zinc could potentially prevent Parkinson’s disease, but warned there could be a few things to keep in mind.

“The HSA site with the strongest affinity for zinc (II) is disrupted by the presence of long-chain fatty acids (FAs),” she said. “When FA levels are elevated during strenuous exercise, fasting, or pathological conditions such as diabetes, it is known to disrupt the physiological binding of zinc to HSA.”

As a result, Al-Harthi explained that zinc would be released from the site and cause cellular stress and side reactions.

“Therefore, the concentration of FA in the blood influences the distribution of zinc, which can affect normal physiological processes and various diseases. Thus, a balanced and healthy diet now seems to have even stronger molecular foundations.

Nancy Mitchell, RN, registered nurse and writer at the Assisted Living Center, said DTM:

“We have to be careful when talking about taking zinc supplements, because ion deficiency and excess can contribute to the progression of Parkinson’s disease. As the study indicates, the exact effect of zinc on our brain health is still being discovered.It can be risky to take supplements without prescribed guidelines, to guard against overdosing on the metal.

Mitchell explained that consuming a diet that includes a variety of whole foods can ensure adequate zinc intake.

“It’s best to rely on a minimally processed diet for zinc intake because there are other natural compounds in foods that play a role in our overall brain health,” she said. declared.

“Isolating just one through a supplement can create imbalances that are also potentially harmful.”

According to Al-Harthi, his team plans to test natural compounds found in the daily diet to study their effect on AS aggregation – which could be used in potential treatments.

“We also want to unlock the diagnostic and therapeutic potential of human serum albumin (HSA), one of the most versatile and challenging proteins in our body,” she said.