ESR4: How does the cytochrome P450 system control drug metabolism in the dopamine neuron?
Jesús Fernández Abascal (University of Siena)
Supervisor: Massimo Valoti
Project summary
Cytochrome P-450 (CYP) is involved in the metabolism of wide-spread exogenous compounds such as drugs and pesticides, i.e. in the brain it activates MPTP to MPP+ in dopaminergic neurons or metabolizes L-deprenyl in mouse microsomes, so it could somehow be linked with the development of Parkinson Disease (PD) by promoting the neurodegeneration of dopaminergic cells.
PD involves several processes that could be metabolically connected with the dopamine pathway biosynthesis, where different alterations in the balance of dopamine metabolism could affect cell homeostasis.
The main goal of the Ph.D. is to study how CYP metabolizes several xenobiotics in dopaminergic cells and elucidate its role in the development of neurodegeneration. The induction of CYP by several drugs could make them be metabolized in new products that could promote neurodegeneration by themselves or even alter the balance of dopamine metabolism.
The specific aims of the project are:
- Effects of neurotoxins on cell lines
- Identification of neuroprotective compounds
- Identification of inducers of CYP expression
- Identification of CYP metabolism metabolites
- Enzymatic activity of CYP in microsomes and mitochondria
Results [top]
In progress.
Outputs [top]
In progress. A review of monoamine oxidases interactions with CYP is being written, with principal investigator Massimo Valoti.
Training [top]
(i) Local level
- Seminar: European funding for research in life science. Daniela Selisca. 1st December 2014.
- Functional Proteomic course. Prof. Luca Bini, from University of Siena. 8th – 11th June 2015.
- Principles of vaccine research & development. Dr. Ahmed Sohail, from GSK Company. 15th- 16th June 2015.
- Seminar: Drug design for monoamine oxidase: enzymology, mitochondria and neuroprotection. Prof. Rona Ramsay, from School of Biology, University of St. Andrews – UK.
Nuclear Magnetic Resonance, Confocal Microscopy and Respirometry. Agilent and Andor Companies. November 2014
Neuronal cell metabolism; and mitochondrial and cellular respiratory physiology. May 2015
Flow cytometry training (6th-7th November 2014)
Respirometry training (5th-6th May 2015)
Outreach [top]
I plan to look for outreach and dissemination opportunities in the next six months. However, I explained to most of the students who are doing their thesis degree at the lab what is the MC ITN programme and invited them to apply for the following calls.
