Thérèse Di Paolo-Chênevert

Prof. Di Paolo is an emeritus professor with more than 300 articles and book chapters published on hormones to protect brain dopamine neurons and the mechanisms of levodopa-induced dyskinesias and their inhibition by drugs of various pharmacological classes. She shows beneficial effects for the brain of endocrine drugs already used in the clinic hence their possible repurposing for Parkinson’s disease (PD). This research has high translational value. Her laboratory was among the first to demonstrate that estrogenic compounds are neuroprotective in animal models of PD 20 years ago. Her group characterized the estrogen receptors involved in the neuroprotection. She also investigated the other ovarian steroid progesterone and found it to be neuroprotective whereas the androgens (testosterone and dihydrotestosterone) were not. She also demonstrated the effects of estradiol on dopaminergic activity in parkinsonian female monkeys. Using different pharmacological approaches, she investigated the estrogen receptors implicated in the beneficial estradiol effects, showing that estrogen receptor alpha and the membrane receptor GPER1 were implicated. Prof. Di Paolo also investigated endocrine drugs that could be repurposed for brain neuroprotection, such as raloxifene, a selective estrogen receptor modulator, and dutasteride a 5α-reductase inhibitor. Importantly, raloxifene was neuroprotective and its effect was mediated mainly by GPER1 receptor. Moreover, dutasteride had brain neuroprotective activity. More recently, she investigated sex-differences in MPTP toxicity and the effects of dutasteride and raloxifene. She has investigated various steroids, including DHEA and pregnenolone. Prof. Di Paolo organized symposia, a special issue of Neuropharmacology in 2019 and was an invited speaker in several international meetings, including Int. Meeting Steroids & Nervous System, Torino, Italy 2024. Considering her experience in PD, Prof, Di Paolo is a section editor for Neuropharmacology since 2018.

Prof. Di Paolo has decades of experience of translational behavioral experiments in MPTP primates as a model of PD and L-Dopa-induced dyskinesias. She uses the MPTP macaque monkey extensively to study numerous compounds of various pharmacological classes (neurosteroids, serotoninergic compounds, kynurenine inhibitors, plasmalogen precursors) with an emphasis more recently on glutamatergic compounds (ionotropic NMDA receptor antagonist, NMDA receptor glycine b site antagonist, metabotropic glutamate receptor 5 negative allosteric modulators, metabotropic glutamate receptor 4 agonist, metabotropic glutamate receptor 4/7/8 agonist). Moreover, she investigates non-pharmacological approaches for PD treatment in MPTP dyskinetic monkeys including a lesion of the subthalamic nucleus, deep brain stimulation, and magnetic stimulation. Moreover, her group was the first to show increased in preproenkephalin expression, GABAA, adenosine A2A, NMDA, AMPA, α7 nicotinic acetylcholine and mGlu5 receptors in brain of PD patients with levodopa-induced dyskinesias.

Prof. Di Paolo’s current and recent funding includes:

• a CIHR project grant with Dr. D. Soulet on the mechanisms of action of sex-specific endocrine treatments in animal models of PD
• MJFox Foundation grant, on the effect of pregnenolone on dyskinesia in monkeys;
• Parkinson Society Canada pilot project on COVID-19 in a PD mouse model;
• a CIHR project grant on the effect of magnetic and pharmacological stimulation on dyskinesia in MPTP monkeys.