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Dimerization of dopamine D3 and acetylcholine nicotinic receptors in the regulation of dopaminergic neurons function: relevance for neurodegeneration in Parkinson's disease
Universita degli Studi di Brescia
Dept of Molecular and Translational Medicine - Pharmacology Unit
Prof. Silvano Sozzani
Dr.Chiara Fiorentini E-mail: firstname.lastname@example.org Phone: +39 030 3717528
Type of Research Project
- Basic science
What is the background of the project?
Dopaminergic neuron function is regulated by different receptors, including the dopamine D2-like receptors (D2R-like), such as the dopamine D3 receptor (D3R) and the acetylcholine nicotinic receptors (nAChR) containing the alpha4 and/or alpha6 subunits and the beta2 subunit. Recent data suggest that D2R-like agonists may slow the progression of Parkinson's Disease and that nicotine has neuroprotective effects on dopaminergic neurons. Morover recent studies report that nicotine regulates dopaminergic neurons neuroplasticity by a mechanism that involves the D3R, suggesting a cross-talk between D3R and nAChR. By using bioluminescence resonance energy transfer (BRET) we found that D3R specifically interact with the Beta2 nAChR subunit suggesting that the D3R/nAChR interaction could be explained by the formation of an heteromeric complex
What is the aim of the project?
The aim of this study is to investigate the mechanisms underlying the interaction between D3R and nAChR-mediated signals. By using interfering peptides to disrupt the interaction between D3R and nAChR we aim to describe the involvement of this heteromeric complex in Parkinson Disease.
What techniques and methods are used?
Cell culture, Western Blot, Immunocytochemistry.
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
What are the tasks expected to be accomplished by the student?
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
No theoretical teaching provided
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
The student should have a good background in neurobiology and pharmacological sciences
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months)
- The D3 dopamine receptor: From structural interactions to function. Fiorentini C; Savoia P; Bono F; Tallarico P; Missale C. Eur Neuropsychopharmacol. 2015 Sep;25(9):1462-9. doi: 10.1016/j.euroneuro.2014.11.021
- Collo G; Bono F; Cavalleri L; Plebani L; Mitola S; Merlo Pich E; Millan MJ; Zoli M; Maskos U; Spano P; Missale C. Nicotine-induced structural plasticity in mesencephalic dopaminergic neurons is mediated by dopamine D3 receptors and Akt-mTORC1 signaling. Mol Pharmacol. 2013 Jun;83(6):1176-89.
- Bono F; Savoia P; Guglielmi A; Gennarelli M; Piovani G; Sigala S; Leo D; Espinoza S; Gainetdinov RR; Devoto P; Spano P; Missale C; Fiorentini C. Role of Dopamine D2/D3 Receptors in Development; Plasticity; and Neuroprotection in Human iPSC-Derived Midbrain Dopaminergic Neurons. Mol Neurobiol. 2017 Jan 14. doi: 10.1007/s12035-016-0376-3.
- Leonardo Bontempi; Paola Savoia; Federica Bono; Chiara Fiorentini; Cristina Missale; Dopamine D3 and acetylcholine nicotinic receptor heteromerization in midbrain dopamine neurons: relevance for neuroplasticity. European Neuropsychopharmacology; 2017 Feb 7. pii: S0924-977X(17)30048-2. doi: 10.1016/j.euroneuro.2017.01.015
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