Funding period: 01.09.2025-31.12.2026
Program: EDUC-WIDE Seed projects
Cooperating Organizations:
Universitá degli Studi di Cagliari – Responsible person assoc.prof. Cristina Cocco – PI of the project
Masaryk University, Faculty of Medicine – Responsible person Amit Suresh Khairnar, Ph.D.
Vasyl Stefanyk Carpathian National University – Responsible person Volodymyr. Shvadchak, Ph.D
Short description:
Parkinson’s Disease (PD) is the second most common neurodegenerative disorder that is yet incurable. It is characterized by loss of dopamine neurons in the substantia nigra and filamentous inclusion of Lewy bodies composed of neuronal protein alpha-synuclein (alpha-syn) misfolded into amyloid fibrils.
The ultimate goal of this project is to develop an approach to decrease the progression of PD by drugs based on VGF peptides. They are neuropeptides produced from the VGF precursor, secreted in neurons (especially in GABAergic), into dense core secretory vesicles and regulated by neurotrophic factors, suggesting a role in neuronal health. The TLQP-24 amidate, TLQP-62, NAPP-19, and TLQP-21 will be chosen among the VGF peptides, based on studies performed at Caglairi University (Italy). This project is a collaboration of 3 research groups to evaluate the protective efficacy of these four VGF peptides by in vitro and in vivo studies.
At Cagliari University, the four selected VGF peptides will be tested in vitro using human and mouse neuronal-induced pluripotent stem cells differentiated in dopaminergic and GABAergic cell lines and treated with the rotenone toxin. Using these cells, the specific cell type expression and levels of VGF peptides in naïve and rotenone-treated cells will be identified by immunohistochemistry and ELISA. Whether VGF peptides could modulate inflammation, stress-related mechanisms, as well as neurotransmitter levels modified in response to rotenone, will also be determined by ELISA and/or qRT-PCR.
Research team at our university will determine the ability of the VGF peptides to bypass the blood-brain barrier when administered intranasally using mice model and perform in vitro studies to test direct effect of the peptides on alpha-syn aggregation using the ThT-based kinetic assay.
Research team, at Masaryk University (Brno, Czech Republic) will work with the most prospective VGF peptide identified in two firs studies and determine its neuroprotective effect of in a progressive intranasal rotenone mouse model.
Results obtained from this study will change the view we are looking at VGF peptides, and our understanding of their poorly understood mechanisms will be expanded. In addition, the knowledge on VGF mechanisms will clarify the molecular events occurring in the early stages of PD. Since there is no medication that can prevent neurodegeneration, if VGF peptides are identified as affecting neurodegeneration in an early phase of PD, this information could be used for research on therapeutic approaches.
Project team at CNU:
Volodymyr. Shvadchak – general coordinator, inhibition kinetic studies
Andrii Shturmak – in vitro inhibitor testing, intranasal delivery experiments
Halyna Cherevata – mice handling and breeding
Halyna Shmihel – administration, presentation of results to general public, etc
Students involved: Nadia Semkiv