Alpha-synuclein protein central to unlocking better dementia cures, researchers suggest

02 Oct 2023 --- Coined the anti-tangle molecule, a fragment of the alpha-synuclein protein has been identified by researchers from the University of Bath and Bristol to prevent tangling of the brain protein linked to Parkinson’s and other neurodegenerative diseases that cause dementia.

The in vitro study’s findings can provide critical insights into new ways of treating or diagnosing the early stages of dementia.

“A major issue with neurodegenerative disease is that diagnosis takes place much too late. We know that disease pathology occurs prior to symptoms, so we need new strategies that can diagnose disease before symptoms present, in addition to molecules that can slow or even halt disease progression,” Jody Mason, professor in the department of life sciences at the University of Bath and lead author of the study, tells Nutrition Insight.

“Currently, drug options for Parkinson’s only treat the symptoms of the disease, often by restoring the lost communication between neurons. Unfortunately, these treatments have side effects, are less effective over time and do not slow the underlying pathology.”

Tweaking protein fragments
The researchers took a protein fragment or peptide from one end of the alpha-synuclein protein strand and mixed it with samples of the full-length alpha-synuclein protein. They discovered that the fragment prevented misfolding in vitro.

“If we could diagnose before symptoms present and block alpha-synuclein misfolding at the earliest stages before clumping, we could slow disease progression instead of just managing the symptoms after the damage has already been done,” Mason explains.

The peptide stabilized the protein strand’s normal structure to prevent it from tangling, forming clumps and disrupting the cell membrane. Alpha-synuclein, found in brain cells, comprises amino acids like all proteins. When made, the strand folds in on itself to form a complex, precise 3D shape of sub-structures and loops.A graphic representation of the solution NMR structure of αS1–25.

In healthy individuals, alpha-synuclein interacts with cell membranes, ensuring neurons communicate. However, as people age, the 3D shape of the protein can malform, sticking together to form toxic clumps. Over time, the clumps stack up, creating fibers that interfere with the normal functioning of the protein, eventually killing brain cells and leading to dementia.

“This in vitro study has demonstrated the potential of this peptide, which we can use as a template to design new drugs that treat the earliest stages of these terrible diseases,” notes Mason.

Earlier this year, a study showed that people consuming a Mediterranean diet had up to 23% lower risk for dementia, independent of genetic risk. 

In addition, several researchers suggest that people who ingest more than 550 mg of magnesium daily have a brain age approximately one year younger at 55 years compared to someone with an average magnesium intake of 350 mg daily. 

In 2022, researchers in Japan explored the potential of iron supplementation on the increased risk of parkinsonism. The longitudinal study found that excessive iron consumption was “significantly associated with higher Parkinson’s risk.” 

Next-gen targeted treatments 
The research, published in the journal Cell Reports Physical Science, opens up new avenues for therapeutic development. One promising pathway is drugs that can target and disrupt alpha-synuclein misfolding and prevent or slow the progression of a disease like Parkinson’s.

The researchers are now seeking funding to continue their research and test different peptide variations on brain cells before identifying suitable candidate molecules for further drug development.

“Our research is still at the early stages, but we hope it’s a stepping stone toward new treatments for neurodegenerative diseases,” says Mason.

Meanwhile, a decade-long study investigating vitamin D and its link to dementia found 40% fewer dementia cases in participants who took dietary supplements compared to the control group. Supplementation was also positively associated with postponing the disease’s development.

By Inga de Jong