Translational development at the interface between diabetes and Parkinson´s disease

Type 2 diabetes mellitus (T2D) and Parkinson’s Disease (PD) are two major disorders associated with aging, and their prevalence is steadily increasing worldwide. These two conditions share several important features: they have a complex multifactorial pathogenesis, encompass different disease subtypes, and are associated with degenerative changes in several organs. Individuals with T2D are reported to be about 30% more likely to develop PD than the general population. However, the relative increase in PD risk conferred by diabetes has varied considerably between studies, possibly depending on disease subtype and duration or severity of the associated metabolic dysfunctions. PD patients with T2D also show faster clinical progression. 

This project will work on the hypothesis that diabetes and PD share important pathogenic pathways and could benefit from shared therapeutic strategies. An altered metabolic state is potentially modifiable, and therapies that mitigate metabolic syndrome factors in T2D are indeed being considered for repurposing to PD. However, it is hitherto unknown what stages of PD pathology or PD symptom clusters would benefit the most from this therapeutic strategy. It is also unknown what types/ combinations of drugs would provide greatest benefit. After identifying which individuals with diabetes are at higher risk of developing PD, we aim to develop a new comorbid T2D-PD mouse model to test neuroprotective and neurorestorative effects of diabetes drugs and to identify biomarkers of disease progression and treatment efficacy. 

IGNITE Fellow - Valentina Cesaroni

Valentina Cesaroni is a postdoctoral researcher at the Diabetes and Brain Function Unit led by João Duarte. She has a strong background in molecular neurobiology, with extensive expertise in rodent behavioral testing, particularly in the context of Parkinson’s disease (PD). She is highly goal-driven and motivated to both acquire new techniques and share her knowledge. She thrives in collaborative environments and brings a positive, energetic approach to her work.

During her Master’s degree in Neurobiology, she acquired strong skills in behavioral neuroscience, particularly with mouse and rat models, as well as in electrophysiology. In January 2020, she earned her PhD in Earth and Environmental Sciences from the University of Pavia (Italy), under the supervision of Prof. Elena Savino and Prof. Paola Rossi. Her doctoral research focused on evaluating the efficacy of a specific medicinal mushroom in mitigating cognitive deficits associated with physiological aging in mice. This work sparked her interest in age-related neurodegenerative diseases, especially Parkinson’s disease.

In November 2019, she joined Prof. Fabio Blandini’s laboratory at the IRCCS Mondino Foundation (Pavia, Italy), where she was tasked with developing a novel mouse model of PD based on pharmacologically induced glucocerebrosidase (GBA) dysfunction. She has since used this model to investigate key PD-related neuropathological changes – including neurodegeneration, neuroinflammation, and alpha-synuclein accumulation – and to assess the resulting behavioral impairments.

In 2022, she was awarded scholarships from the Lerici Foundation, Blanceflor Foundation, and Wenner-Gren Foundation, which enabled her to join the Basal Ganglia Pathophysiology Unit at Lund University, led by Professor Angela Cenci Nilsson. Since then, she has been involved in several innovative projects focused on understanding and characterizing the pathophysiological mechanisms triggered by the seeding and spreading of alpha-synuclein pathology in the brain. This experience has significantly deepened both her interest and expertise in complex behavioral analyses in rodent models. It has also allowed her to broaden her scientific knowledge in the Parkinson’s disease field and gain hands-on experience with advanced PD models. She is currently using these models to develop and evaluate pharmacological treatments aimed at alleviating symptoms and slowing disease progression through neuroprotective, anti-inflammatory, and plasticity-enhancing mechanisms.

Her experience supervising bachelor’s and master’s students, organizing outreach activities such as workshops and being part of committees and group management, has strengthened her ability to effectively communicate complex scientific ideas and work in interdisciplinary environments.

Her current research focuses on investigating molecular mechanisms and therapeutic strategies relevant to individuals with comorbid type 2 diabetes mellitus (T2D) and Parkinson’s disease (PD), including Parkinson’s disease with dementia (PDD). Individuals with T2D have a 30% higher risk of developing PD and tend to experience a more rapid disease progression. The central hypothesis of her project is that T2D and PD share key pathogenic pathways and may benefit from overlapping therapeutic interventions. A second aim of the project is to identify metabolomics-based biomarkers for monitoring treatment responses in individuals affected by both conditions. She is enthusiastic about contributing to this interdisciplinary project, which explores the molecular links between metabolic dysfunction and neurodegeneration.

Main Principal Investigator

• João Duarte

Co-supervisor

• Angela Cenci Nilsson