Interview with Prof. Kujawska, "Graphene dots may help fight Parkinson's protein clumping"

Professor Małgorzata Kujawska, PhD, DSc, is an expert in toxicology and nanoneuroscience at the Poznan University of Medical Sciences, Poland, specializing in synucleinopathies and the potential of nanomaterials in managing these pathologies. She has experience in European research initiatives and EU grant evaluation, shaping advancements in nanotechnology-driven innovations and nanotoxicology. She leads the interdisciplinary Nano4Med Research Group and holds the title of European Registered Toxicologist (ERT).
 

The path to this research

Q1: What earlier findings led you to focus on graphene quantum dots as anti-aggregation agents for α-synuclein? Was there a specific moment (a study or a lab observation) that first sparked this hypothesis?

Małgorzata: This idea was inspired by a broader exploration for new disease-modifying approaches in Parkinson's disease and other synucleinopathies, and our critical review of the literature
(https://pubs.rsc.org/en/content/articlelanding/2023/ma/d3ma00623a) 
supported graphene-based materials as a potential, but underexplored, avenue for addressing α-synuclein pathology. Together with my colleague Dr. Piotr Chmielarz, we designed a screening scheme for comparing in this context various graphene-based nanomaterials. Thus, there was no single "eureka" moment and the hypothesis developed step by step.

Q2:What gap in the existing literature did this study set out to fill — particularly regarding GQD behavior in models beyond cell-free assays?

Małgorzata: Most published data on GQDs and α-synuclein come from cell-free assays and computational simulations, with very few studies in disease-relevant cellular or animal models, and none — to our knowledge — in a model of multiple system atrophy. Given the differences in material characteristics across studies, understanding how physicochemical properties relate to biological effects remains an important challenge.

Findings, impact and relevance

Q3:Your multi-stage approach — from cell-free assays to intranasal administration in MSA mice — yielded promising results. How do they compare with what other groups working on nanomaterial-based strategies have reported?

Małgorzata: Computational and experimental studies have shown that graphene-based nanomaterials can disrupt α-synuclein aggregation, but experimental works beyond cell-free assays are few, and results in this field are highly dependent on a combination of variables, including nanomaterial, model, and experimental conditions, making direct comparison difficult, thus underscoring the importance of thorough characterization alongside biological evaluation.

Q4. What are the most critical hurdles — biocompatibility, delivery, stability — before GQDs could be considered in any clinical context?

Małgorzata: We are still at the stage of building a fundamental understanding and it is too early to speak about clinical applications. Reproducible synthesis and the tendency of GQDs to form aggregates remain key obstacles.

In ongoing collaboration with the Maj Institute of Pharmacology, we are currently developing approaches to address these challenges. Equally important is a comprehensive understanding of GQD safety — especially which variables determine its safety profile.

Furthermore, the cellular and subcellular fate of GQDs — their uptake, intracellular distribution, and clearance — remains largely unexplored, and clarifying this is essential for any future translational considerations. Last, but not least, delivery remains a challenge: not only to the brain, but also in the context of a synucleinopathy that does not necessarily originate in the brain.

Q5. In plain terms, why does it matter that a nanoscale carbon particle can interfere with protein clumping in the brain? What does this mean for patients?

Małgorzata: For patients, this means that research is moving forward, but translating these findings into any form of therapy requires years of further work. Short-term studies targeting A-synuclein in synucleinopathies have not shown clinical efficacy; however, it has been announced that in long-term (5-year) follow-ups, antibodies targeting aSynuclein slowed down motor decline in PD patients. This demonstrates that clinical trials for slow neurodegenerative disease are extremally complex, while treatment will have to be administered for years or decades, clearly pointing to need of extremally safe, and easy to administer therapeutics.

The scientists behind the research

Q6. Your study seems to suggest GQDs could be relevant beyond synucleinopathies, for other proteinopathies as well. Is this a direction your group is actively pursuing, or still a distant hypothesis?

Małgorzata: A logical extension of this would be other proteinopathies, but that is not where we are. The next logical step is to expand within the synucleinopathy space, including models that incorporate pathology outside of the brain. The first step is to go deep before you go wide.

Q7. What is the most intellectually exciting aspect of this work for you personally?

Małgorzata: It is the interface, where materials science and neurobiology intersect, especially regarding how nanomaterials interact with oligomeric forms of α-synuclein, which are recognized as the most toxic and challenging species. That is where the real answers lie.

Q8. Can you share a turning point in your career — a moment that changed the way you approached a problem?

Małgorzata: There was no one turning point, but a systematic deepening, with each study showing how much more there is to investigate, if anything, the most important realization was that the closer you look at the nano–bio interface, the broader the spectrum of unanswered questions.

Q9. What originally drew you to toxicology and neuropharmacology?

Małgorzata: Toxicology is the science of drawing the line between what heals and what harms. Neurodegenerative diseases are full of open questions on both sides of that line, such as what causes the disease and whether what we develop as treatment is truly safe.