SK-129 aims to prevent formation of toxic protein clumps
Written by Patricia Inácio, PhD | April 8, 2026
- Parkinson's and related diseases involve toxic alpha-synuclein protein clumps.
- SK-129, a lab-made molecule, reduced these toxic protein clumps and their spread.
- It crossed the blood-brain barrier, showing promise for slowing disease progression.
A small, lab-made molecule called SK-129 reduced the formation of toxic clumps of the alpha-synuclein protein, a hallmark of Parkinson’s disease, a study found.
SK-129 was able to cross the blood-brain barrier – a semipermeable membrane that protects the brain and central nervous system – and prevent damage caused by these toxic clumps, as well as their spread across the brain.
The findings may also be relevant to other Parkinson’s-like diseases characterized by abnormal clumping of the protein alpha-synuclein, including Lewy body dementia and multiple system atrophy.
“This is an important step toward developing treatments that target the root cause of these diseases,” Mazin Magzoub, PhD, associate professor of biology at NYU Abu Dhabi and a co-lead author on the study, said in a New York University press release. “Instead of only treating symptoms, we are working toward slowing or stopping the disease itself.”
The study, “Foldamers rescue synucleinopathy phenotypes in multiple in vitro and in vivo models,” was published in the journal Science Translational Medicine.
Misfolded protein forms toxic clusters
Parkinson’s disease is caused by the progressive loss of dopamine-producing neurons, a type of nerve cell important for movement control.
A hallmark of Parkinson’s and related disorders, collectively known as synucleinopathies, is the formation of toxic clumps of the protein alpha-synuclein in brain cells. In healthy neurons, alpha-synuclein normally exists in a monomeric (single-molecule) form and is involved in nerve cell communication.
But when the protein misfolds, it can assemble into small toxic clusters called oligomers, which then form larger aggregates that make up Lewy bodies, a key disease-causing feature of Parkinson’s. These clumps contribute to cell death and spread in a prion-like manner, meaning aggregates in one brain region may trigger more misfolding in nearby regions.
That means preventing alpha-synuclein from clumping and spreading is seen as a promising strategy for treating synucleinopathies.
Researchers at NYU Abu Dhabi and the University of Denver focused on the potential of foldamers, lab-made molecules designed to mimic features of natural proteins. Specifically, they investigated SK-129, a foldamer designed to inhibit alpha-synuclein aggregation.
In lab tests, they found that SK-129 blocked alpha-synuclein from clumping together and reduced disease-related effects across several lab models, including nerve cells derived from human induced pluripotent stem cells (iPSCs) and animal models such as the worm Caenorhabditis elegans and mice. iPSCs are cells that can generate almost any type of cell in the body.
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