‘Opioid Of The Masses’ Used To Make Therapies For Neurodegenerative Diseases

By Deborah Borfitz 

January 24, 2024 | Taking a cue from Mother Nature, researchers from The University of Texas at El Paso are exploring the use of carbon nanoparticles synthesized from caffeic acid found in coffee grounds as a preventative or therapeutic agent for neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Their work marks the first time caffeic acid has been used to create carbon quantum dots and the approach is not only economical and sustainable but also potentially interventional, according to Mahesh Narayan, Ph.D., a professor and Fellow of the Royal Society of Chemistry. 

In a recently published study appearing in Environmental Research (DOI: 10.1016/j.envres.2023.116932), the novel caffeic-acid based carbon quantum dots (CACQDs) protected a human neuroblastoma cell line with induced phenotypic Parkinsonism from the damaging effects of paraquat, a widely available herbicide. They also prevented protein aggregation and scavenged free radicals, two “independent outputs on the trajectory of [neurodegenerative] pathology,” says Narayan. 

The disease-modifying potential of CACQDs is not what makes them unique—it’s the simplicity of creating them, he adds. The process involves cooking caffeic acid extracted from otherwise wasted coffee grounds at 200 degrees for four hours to get the desired carbon structure, and the researchers also use ultrapure water in lieu of organic solvents in the creation of the CACQDs, both of which qualify as “green chemistry.”  

Production of the CACQDs is sustainable because coffee is the “opioid of the masses” and is thus likely to be around for centuries to come, Narayan says. To ensure reproducibility, investigators used caffeic acid produced by Sigma-Aldrich for study purposes. The caffeic acid content of coffee varies widely from brand to brand, he notes. 

Narayan is one of a larger group of researchers who has spent years experimenting with nutraceuticals, such as curcumin (the active ingredient in turmeric), which have repeatedly failed in clinical trials for one of two reasons, he says. “Either they fail to cross the blood-brain barrier, or the laboratory models of the pathology do not mimic human pathology to the extent that we’d like.”  

Scientists have been working with carbon quantum dots for the past decade, says Narayan. He was introduced to them about five years ago by a graduate student who had experience synthesizing them in another lab. 

At the time, caffeic acid wasn’t one of the carbon sources being used to make quantum dots, he continues. But on its own, it had been associated with antioxidant, anti-inflammatory and anticarcinogenic activity.  

Creation of the CACQDs was intended to strengthen those effects, since some of the functional groups of caffeic acid are retained, which is advantageous for penetration of the blood-brain barrier. The caffeic acid was recarbonized using hydrothermal synthesis, widely used to make carbon quantum dots, to “one up the system,” says Narayan.  

Disease Modeling

Except for Huntington’s disease, which is an inherited condition, 95% of people with neurodegenerative disorders have sporadic or idiopathic forms of the disease, says Narayan. That means there is no known cause, only risk factors such as exposure to environmental and industrial toxins, consuming a lot of processed food, leading a sedentary lifestyle, and plaque buildup—all modifiable risks factors.  

In the preclinical study setting it would be unfeasible to wait for Parkinson’s or Alzheimer’s disease to set in naturally in either a cell line or animal model. “In a cell line, of course, we don’t have tremor as is found commonly in humans and animals... [and] there is no memory,” he says. 

Narayan and his team therefore used paraquat, readily available in the form of herbicides and weedicides at commercial lawn and garden stores, to induce the Parkinsonian phenotype—characterized by protein accumulation, mitochondrial dysfunction, reactive oxygen species elevation, neuronal injury, and eventual neuronal demise—in a cell line long ago immortalized from human neurons, he explains. 

When the CACQDs were introduced into the cell line, they stopped the process of protein aggregation in a hen egg white lysozyme (HEWL) model, what Narayan calls “a poor man’s amyloid beta.” Aggregated proteins cause neurodegenerative disease, as was discovered by 1997 Nobel Prize winner Stanley Prusiner, and that applies to Parkinson’s (amyloid fibrils of alpha-synuclein) as well as mad cow disease (prion), Alzheimer’s (amyloid beta and tau), and Huntington’s disease (mutant huntingtin).  

The CACQDs were found to intervene in the formation of fibrils in the HEWL model by preventing the soluble-to-toxic conversion of amyloid proteins, as well as to mitigate cell mortality arising from paraquat-induced elevation in reactive oxygen species. Both suggest its potential for prevention of neurodegeneration, says Narayan. 

Quantum dots aren’t going to help once critical side effects—e.g., impaired diaphragmatic function and difficulty swallowing and speaking—set in, he adds. However, next steps for the research team includes testing to see if CACQDs can penetrate the blood-brain barrier and perhaps be a candidate therapeutic. 

It’s a strong possibility, since caffeic acid already crosses the blood-brain barrier naturally, says Narayan. “We hijacked nature, in a sense.”   

Future experiments will need to be conducted in rats as opposed to a worm model of Parkinson’s and Alzheimer’s diseases. The worms are not a good model for the required cognitive testing, says Narayan.  

Answers have been slow in coming for people with, or at risk for, neurodegenerative diseases. A biologic (Aduhelm) is now on the market to reduce the buildup of amyloid beta plaque seen with Alzheimer’s disease, and deep brain stimulation is available for patients with Parkinson’s to lessen motor symptoms of stiffness, slowness, and tremor. But both treatment options are unaffordable for most people, he says.  

If CACQDs work as well as he hopes in rat models, Narayan says he will be looking for a mom-and-pop company with the wherewithal to conduct clinical trials and scale up production of the carbon nanoparticles. “Sometimes a cure, or a preventative, is right in front of our eyes... [like] your cup of joe.”