Title : Functional characterization of a novel selenoprotein in a neurodegenerative disease model
Abstract:
Neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease (PD) are progressive conditions that affect the nervous system. All these diseases are characterized by the progressive loss of neurons in more or ess localized regions of the nervous system, leading to cognitive, motor, or perceptual complications. PD is characterized by selective and progressive degeneration of dopaminergic neurons located in the substantia nigra pars compacta (SNc) and their nerve endings, which normally release dopamine in the striatum. Although the exact causes of PD are unknown, numerous studies have demonstrated the important role of oxidative stress in the degeneration of dopaminergic neurons. Moreover, high levels of free radicals are observed in the brains of post-mortem patients. These observations suggest that proteins that play a role in protecting neurons from the effects of oxidative stress may represent interesting therapeutic targets. In fact, to maintain redox balance, cells recruit several reducing enzymes, including members of the selenoprotein family. Previous studies have shown that selenoprotein T (SelT), a new selenoprotein identified in nerve cells, is highly expressed in conditions of neuronal degeneration following oxidative stress and plays a neuroprotective role. This role is performed by its active site containing cysteine and selenocysteine. The aim of my thesis is to characterize the therapeutic use of a new peptide derived from selenoprotein T, called PSELT, containing the active core of SelT as a neuroprotective treatment in PD. PSELT will be tested in vitro model of PD, using SH-SY5Y neuroblastoma cells, and in vivo in a model of PD in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The use of these models will allow us to determine the optimal dose and route of administration of the PSELT peptide, to study its mechanisms of action on free radical levels, neuronal survival, apoptosis, and ultimately its action on the motor symptoms characteristic of this complex and debilitating disease.
