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October 30, 2020 04:00am
By Jennifer Gershman, PharmD, CPh
The caffeine-based compounds could prevent the misfolding of Î±-synuclein.
Results from a recent study suggest that caffeine-based chemical compounds could potentially treat Parkinson’s disease.
Parkinson’s disease affects the nervous system, and can cause shaking, muscle stiffness, and slow movements. It results from losing brain cells that make dopamine.
In the study, published byACS Chemical Neuroscience,researchers examined the protein α-synuclein, which is involved with dopamine regulation and becomes misfolded in patients with Parkinson’s disease.
The misfolding of 1 α-synuclein can trigger the misfolding of others and spreads. A similar occurrence happens in patients withamyloidosis diseasessuch as Alzheimer’s disease. The misfolded proteins are distributed throughout the body and can be deposited in the heart, liver, retina, and other organs.
Preventing the misfolding of α-synuclein is the main goal of the current strategy to protect against the disease.
“Many of the current therapeutic compounds focus on boosting the dopamine output of surviving cells, but this is effective only as long as there are still enough cells to do the job,” said Jeremy Lee, BSc, PhD. “Our approach aims to protect dopamine-producing cells by preventing α-synuclein from mis-folding in the first place.”
The researchers synthesized 30 bifunctional dimer drugs, which link 2 different substances that can affect dopamine-producing cells, according to the study. Since there have been previous studies that suggest caffeine can be protective against Parkinson’s disease, researchers started with a caffeine structure.
They then added other compounds, such as nicotine, metformin, and the experimental drug aminoindan. Aminoindan is similar to rasagiline, a Parkinson’s disease drug.
When the compounds were tested in a yeast model of Parkinson’s disease, they discovered that the 2 caffeine-based compounds prevented the misfolding and clumping of α-synuclein. This would allow the cells to grow normally, according to the study.
“Our results suggest these novel bifunctional dimers show promise in preventing the progression of Parkinson's disease,” Dr Lee concluded.