Please click here for PubMed citations for Dr Hickey.

Nanoparticle delivery of curcumin for Alzheimer's disease
Many promising natural compounds cannot be used as medicines because they are poorly absorbed by the body, or are well absorbed but are then rapidly broken down before reaching the brain. In this study, our collaborators developed a nanoparticle-based delivery system that packages curcumin—a natural anti-inflammatory compound from turmeric—inside tiny ferritin protein nanoparticles. They showed that these nanoparticles were stable, non-toxic and able to cross a laboratory model of the blood–brain barrier far more effectively than curcumin alone. They also showed that in immune cells from people with Alzheimer's disease, the treatment reduced inflammatory signalling. As part of this international collaboration, we demonstrated that our curcumin delivery system reduced activation of inflammatory brain cells (microglia and astrocytes) and produced mild improvements in cognitive function in a mouse model of Alzheimer’s disease. These findings demonstrate the potential of nanotechnology to improve delivery of therapies to the brain and support further development of ferritin nanocages as a platform for treating neurodegenerative diseases. Paper is here.

Levodopa impairs lysosomal function in sensory neurons
Levodopa remains the most effective treatment for the movement symptoms of Parkinson's disease, but some patients develop problems with sensation at high doses or after being on the medication for a long time. These sensory problems include peripheral neuropathy. We investigated how levodopa itself could affect the health of sensory nerve cells, the cells that allow us to sense heat, cold, touch, pressure. Using primary sensory neurons and a sensory neuronal cell line, we found that exposure to high-dose levodopa impaired the function of lysosomes—the cell's recycling system—and reduced mitochondrial health, both of which are essential for maintaining healthy neurons. Importantly, these effects occurred at drug concentrations similar to those seen in patients receiving high-dose levodopa and were not explained by levodopa's breakdown into homocysteine, which had previously been suggested as the cause of nerve damage. Our findings provide new insight into why sensory symptoms may worsen in some people receiving long-term levodopa treatment and highlight lysosomal function as a potential target for protecting peripheral nerves in Parkinson's disease. Paper is here.

Early sensory nerve dysfunction in Wolfram syndrome
Wolfram syndrome is a rare inherited neurodegenerative disease that causes diabetes, blindness and progressive neurological problems, but little is known about why many patients also experience trigeminal neuralgia-like pain and altered sensation. Using two complementary animal models, together sensory neurons and data from patient-derived cells, we showed that sensory nerves begin to deteriorate early in the disease. We found shrinkage of the trigeminal nerve pathway, impaired function of sensory neurons and defects in lysosomes—the structures responsible for recycling damaged material within cells. Similar lysosomal abnormalities were also identified in patient-derived cells. These findings reveal that sensory nerve dysfunction is an early feature of Wolfram syndrome and suggest that restoring normal lysosomal function could be a promising new strategy for slowing nerve degeneration. Paper is here.

Traditional models of Parkinson’s disease do not model the entire disease
Parkinson's disease (PD) is best known for causing movement problems, but patients also experience many non-motor symptoms, including constipation, sleep disturbances and changes in sensation. Researchers commonly study PD by using toxins to damage dopamine-producing neurons in the brain, reproducing the movement problems seen in patients. However, in this study we showed that these traditional models fail to reproduce several important non-motor features of the disease. The animals did not develop constipation or changes in sensory function, despite showing clear movement deficits. Our findings suggest that these models may not be the best choice for testing new therapies aimed at treating the full range of symptoms experienced by people with Parkinson's disease and highlight the importance of developing models that better reflect the whole disease. Check our paper here.

Improving the quality of Alzheimer's disease research
Many potential Alzheimer's disease treatments show promise in animal studies but fail when tested in patients. One reason is that preclinical studies sometimes use too few animals or rely on measures that are too variable to detect meaningful treatment effects. In this study, we carefully examined how behavioural tests and brain pathology change throughout the progression of disease in the widely used 5xFAD mouse model of Alzheimer's disease. We identified which measures are the most sensitive and reliable at different stages of the disease and calculated the number of animals needed to detect realistic treatment effects. These findings provide practical guidance for designing more robust and reproducible preclinical studies, helping researchers develop better therapies while reducing unnecessary animal use. Paper is here.

Also check out our recent reviews on curcumin formulations for AD and on rotenone's pharmacokinetics, and our editorial on Mild cognitive impairment and cognitive aging.

Image

Basic science research

Why does stress increase the risk of Parkinson's disease?

Parkinson's disease is a progressive neurological disorder that affects millions of people worldwide. While some people develop PD because of inherited genetic changes, the causes of most cases remain unknown. Researchers believe that the disease may result from a combination of genetic and environmental factors, many of which are still not fully understood.

One intriguing finding from recent large-scale studies is that people with long-term depression or anxiety have a substantially increased risk of developing Parkinson's disease years, or even decades, later.

Our research aims to understand why.

Stress affects many biological systems throughout the body and influences the function of many different types of cells. We are particularly interested in understanding how stress affects the cell's "recycling system", known as the lysosome. Lysosomes play a vital role in breaking down damaged proteins and other cellular waste, helping to keep cells healthy and functioning properly.

To investigate this, we will use well-established laboratory models of PD carrying the same genetic changes that cause or increase the risk of PD in people. We will then study how stress influences the earliest changes associated with PD, not only in the brain but also in the gut and nervous system, where evidence suggests the disease may begin many years before symptoms appear.

By combining data from our genetically relevant laboratory models with large datasets from patients with Parkinson's disease, we hope to identify the biological pathways that link chronic stress to Parkinson's disease. Ultimately, this research could improve our understanding of why some people develop the disease and identify new opportunities for earlier diagnosis and treatment.

Ultimately, this research could improve our understanding of why some people develop the disease and identify new opportunities for earlier diagnosis and treatment. Listen here.

Image

Teaching research

Interprofessional education for safer prescribing

Effective healthcare depends on doctors, pharmacists and other healthcare professionals working together. To help prepare future clinicians for this reality, we developed an interprofessional learning experience that brings together medical and pharmacy students to solve real-world prescribing challenges using our digital prescribing platform, Student eScript (see more below).

Students work collaboratively to review prescriptions, identify potential problems and discuss how communication between healthcare professionals improves patient safety. This approach helps students develop prescribing skills while gaining a better understanding of the complementary roles of different healthcare professions.

As part of our ongoing educational research, we evaluate this teaching innovation through an ethically approved student survey to better understand its impact on learning. This initiative has been well received by students and demonstrates how innovative teaching can strengthen clinical education.

Despite being developed with limited resources and a small faculty team, the project was presented at the European Association of Faculties of Pharmacy (EAFP) Annual Conference 2026 and contributes to the University of Tartu's ongoing development of the medical curriculum by promoting digital learning, interprofessional collaboration and practice-based prescribing education.

Collaboration: Dr Külli Jaako, Department of Pharmacology

Classroom teaching

Dr. Hickey is responsible for and teaches "Basic Pharmacology and Toxicology" to medical undergraduates of the University of Tartu Medicine via English program. This course welcomes visiting students!

She also teaches as guest lecturer in courses such as “Research Work for Students”.

Basic science research

Peripheral nervous system involvement in Parkinson’s disease

Image

Left: Cultured sensory neuron expressing a calcium-sensitive dye. Middle: Cultured sensory neurons (green). Nuclei are shown in blue. Right: Sensory neurons (brown) in pinna skin. e, epidermis; d, dermis; c, cartilage layer.

In a collaboration with Dr Pille Taba (Estonian Research Council “Team grant" project PRG957), the Chair of the Neurology Clinic at Tartu University Hospital, we plan to examine “Peripheral nervous system involvement in Parkinson's disease”.

Parkinson’s disease is the most common neurodegenerative movement disorder, and it shows a prevalence of 1.3% in individuals over the age of 60 in Estonia(1). Worldwide, it is the second-most common neurodegenerative disease, after Alzheimer’s disease.

The most prevalent movement disorder of Parkinson’s disease (PD) is slowness. For example, when asked to tap their fingers together, patients show a slower tapping rate. Tremor is often seen, where the fingers, the hand or limb shake when at rest. The other classic PD movement disorder is muscle stiffness.

PD also causes many more problems that we term “non-motor”. Some of these non-motor signs include constipation and a loss of sense of smell. We now know that these symptoms can occur many years prior to the slowness of movement.

The classical pathology associated with PD is the loss of dopamine neurons in a region of the brain called the Substantia nigra pars compacta (SNpc). In addition, aggregates of the protein alpha synuclein are found in brain. These aggregates are called Lewy bodies. However, Lewy bodies are also found outside the brain, in the periphery, and they can be found many years prior to diagnosis.

Interestingly, sensory neurons in skin, the neurons that detect touch, heat and cold for example, develop Lewy bodies. Dr Taba’s group recently reported changes in gene expression in samples of skin from PD patients(2). Excitingly, some of these changes included increased expression of ion channels and receptors expressed by these neurons.

Expression of these channels is increased in animal models of peripheral neuropathy, and intriguingly, PD patients also develop peripheral neuropathy but this symptom is little studied and its mechanism is not understood.

In this collaboration, we will examine peripheral neuropathy using parkinsonian peripheral neurons and established animal models of PD. These experiments will complement studies of peripheral neuropathy in PD patients, by Dr Taba’s group.

Ultimately, we hope that our work will help find therapeutic targets for the development of treatments for this underdiagnosed and undertreated peripheral sign in PD.

Check out our recent review here our recent paper here.

• (1)Kadastik-Eerme, L., Taba, N., Asser, T. & Taba, P. The increasing prevalence of Parkinson’s disease in Estonia. Acta Neurol. Scand. 138, 251–258 (2018).
• (2)Planken, A. et al. Looking beyond the brain to improve the pathogenic understanding of Parkinson’s disease: implications of whole transcriptome profiling of Patients’ skin. BMC Neurol. 17, 6 (2017).
  

Image

Ferritin nanocages based on curcuminoids for anti-aging treatment

Image

Left: Astrocytes, shown in red fluorescence, in cortex of a mouse model of Alzheimer's disease. Right: Microglial cells, shown in brown, in cortex of a mouse model of Alzheimer's disease.

In a collaboration with Dr Fabio Corsi, Dr Cristina Cereda both of the Istituti Clinico Scientifici Maugeri S.p.A. Società Benefit, Pavia, Italy, Dr Aristidis Tsatsakis of the University of Crete and Dr John Cashman of the Human Biomolecular Research Institute, California, we are examining whether ferritin-nanocages can improve delivery of curcumin to brain, in a project funded by EuroNanoMed III.

Cucumin, the major part of Turmeric, the spice we use in our curries, is a naturally occurring polyphenol. But for many years, it has also been known as an anti-amyloid.

Build-up of amyloid in brain is classically associated with Alzheimer’s disease, the most common neurodegenerative disease worldwide. However, amyloid has been shown to be present in the brains of patients with AD many years prior to diagnosis. Thus, to reduce amyloid, earlier treatments that are safe are required and indeed, Curcumin is known as “GRAS” (generally recognized as safe).

When we eat Curcumin, it is metabolised extensively and very little (<5%) of the parent molecule remains in the body. Some of these metabolites are biologically active but because they are less lipophilic than Curcumin, they are prevented from entering the brain.

In this collaboration, Dr Corsi and Dr Cereda’s groups will encapsulate curcumin in ferritin-nanocages, which are made from ferritin monomers, a naturally occurring protein in the body. These nanocages are known to cross the blood-brain-barrier. Dr Tsatsakis’ group will examine the toxicology of these nanoparticles. We will examine whether these nanoparticles increase delivery of curcumin into brain and if they can reduce AD-related neuropathology using an established animal model of AD.

Together, we hope to safely reduce amyloid burden in brain.

Please see our recent review here.

Gagliardi S, Morasso C, Stivaktakis P, Pandini C, Tinelli V, Tsatsakis A, Prosperi D, Hickey M, Corsi F, Cereda C. Curcumin Formulations and Trials: What's New in Neurological Diseases. Molecules. 2020 Nov 18;25(22):5389. doi: 10.3390/molecules25225389. PMID: 33217959; PMCID: PMC7698610.

Please see our paper on sample-size calculations for pre-clinical research here. This is a vital part of working with models of diseases, and helps plan better experiments and therapeutic trials.

Faisal M, Aid J, Nodirov B, Lee B, Hickey MA. Preclinical trials in Alzheimer's disease: Sample size and effect size for behavioural and neuropathological outcomes in 5xFAD mice. PLoS One. 2023 Apr 10;18(4):e0281003. PMID: 37036878 PMCID: PMC10085059 DOI: 10.1371/journal.pone.0281003

Image

Development of curricula via international collaboration

Iceland has a population of almost 340 000, and Estonia, just over 1 316 000. These two small countries on the opposite borders of the European Union face similar challenges when attracting and educating the best of their young minds due to a lack of resources and a lack of flexibility for their students.

In this cooperation program, funded by Iceland Liechtenstein Norway Grants, medical undergraduates from the University of Tartu (UT) will visit the University of Iceland (UI) and UI medical undergraduates will travel to UT, for 1 month, to complete mini science projects, for credits. While in Iceland, students will work with Professor Þór Eysteinsson and while in the University of Tartu, students will work with Dr Hickey and Dr Monika Jürgenson both of the Department of Pharmacology at UT.

In this program, the miniprojects that we offer to our undergraduate students will cover a wide range of topics, and the techniques offered will be cutting edge and unique to each participating university. By focusing on preclinical research in these miniprojects, we hope to expose our medical undergraduates to the importance of basic science.

Importantly, through this cooperation, we will provide our undergraduates with opportunities for internationalisation, to form new collaborations, to learn new hard skills and critically, this cooperation will provide our undergraduates with opportunities for development of their transferable skills. These opportunities are in line with the guidelines set out by the Estonian Ministry of Education and also frameworks guiding modern medical undergraduate education.

Have a look here for more information and a short video introducing our program.

Image

14th Oct 2023, in Biomedicum (Ravila 19, Tartu)

Please also see here for more information about Tartu-Iceland Research Exchange Program.

Image

Image

Development of an online student prescribing tool

More and more healthcare systems are using digital prescribing. Funded by a University of Tartu Good Teaching grant (2018-2020), and together with partners Alina and Indrek Altpere of Upload OÜ, we have developed Student eScript.

Student eScript is a novel, online, student, prescribing-only tool for medical students.

It is designed to assist learning of drug side effects, drug metabolism, drug interactions and much more. Student eScript contains simple case studies, a student formulary based on course content, and provides "real-world“ experience for learning purposes.

Please see here for more information on Student eScript. Student eScript is fully adaptable to any course requirements. It enables the lecturer to provide feedback and marks, and access is controlled by the course provider. Ask for a demonstration today!

Image