Cellular and molecular neurobiology

This unit’s research activity focuses on Parkinson’s disease (PD). Its general aims are to investigate the pathogenetic mechanisms of the disease and identify neurochemical parameters (biomarkers) correlated with its onset and/or progression, and linked to the presence of risk factors (e.g., mutations in the GBA gene), which might be used in clinical practice and in the development of personalized therapies. To this end, the Unit uses animal and cell models, but also (thanks to its close collaboration with the clinical units) biological samples (e.g., blood, skin biopsies) obtained from patients with PD.

For its animal research, the Unit uses traditional disease models based on intra-cerebral (stereotaxic) or systemic administration of neurotoxins, such as 6-hydroxydopamine and MPTP, and has recently developed a PD mouse model that shows reduced activity of the glucocerebrosidase enzyme, comparable to that observed in parkinsonian patients with GBA mutations. The animal studies are conducted with the aim of investigating the role of neuroinflammatory processes, oxidative stress and proteo-toxicity in the development of the neurodegeneration, and gastrointestinal system changes that characterize the disease, and of evaluating new treatment strategies — both pharmacological and non- pharmacological — aimed at modifying its evolution.

With regard to the identification of potential biomarkers, changes in lymphocytes isolated from peripheral blood and fibroblasts obtained from skin biopsies are currently being investigated, as is the presence of pathological proteins (e.g., alpha-synuclein, tau) in extracellular vesicles (exosomes) derived from plasma. These activities are carried out as part of research projects with various sources of funding, such as the Italian Health Ministry, under its “Current Research” (Ricerca Corrente) and “Targeted Research” (Ricerca Finalizzata) programs, the Italian Universities and Research Ministry (MIUR), the European Commission, the Italian Medicines Agency (AIFA), the COEN (Centers of Excellence in Neurodegeneration), JNPD (EU Joint Programme – Neurodegenerative Disease Research) and ASAP (Aligning Science Across Parkinson’s) initiatives, and banking foundations.

Specialized equipment:

• Odyssey Infrared Imaging System (Li-Cor) for immunochemical imaging
• Stereology system and analysis software(MicroBrightField)
• CLARIOstar fluorescence / luminescence / absorbance microplate reader(BMG LABTECH)
• Stereotaxic apparatus for small animals(Stoelting)
• Rotarod for evaluating motor function in animals (PANLAB)
• Motorized M2 direct light/fluorescence microscope (Zeiss) with image analysis software
• ApoTome Zeiss system for high-definition reconstruction of microscopy images
• Nanosight NS300 equipped with NTA technology for the analysis of nanoparticles
• Seahorse XF Analyzer (Agilent) for the analysis of mitochondrial energy metabolism