Article
Neurosciences
Yuhao Yuan, Xiaoqian Zhang, Yi Wu, Piaopiao Lian, Xuebing Cao, Yan Xu
Summary: This study examined the effects of an astrocyte regulator (ONO-2506) on levodopa-induced dyskinesia (LID) in a rat model of Parkinson's disease. The results showed that ONO-2506 significantly delayed the development of LID in the early stage of L-DOPA treatment. However, it had no significant effect on motor function improvement. The study suggests that interventions targeting astrocytes and glutamate transporters may be potential therapeutic strategies to delay the development of LID.
Article
Neurosciences
Rafael Rivas-Santisteban, Alberto Jose Rico, Ana Munoz, Ana I. Rodriguez-Perez, Irene Reyes-Resina, Gemma Navarro, Jose Luis Labandeira-Garcia, Jose Luis Lanciego, Rafael Franco
Summary: This study reveals the antagonistic effect of adenosine on dopaminergic transmission in the basal ganglia indirect motor control pathway. The interaction between A2AR and D2R receptors plays a crucial role in regulating dopamine signaling. A2AR blockers have shown efficacy in alleviating symptoms of Parkinson's disease. Additionally, the number of interacting receptors increases in animal models of Parkinson's disease, suggesting the potential benefits of early treatment targeting the adenosine receptor.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Antonio Abad-Garcia, A. Lilia Ocampo-Nestor, Bhaskar C. Das, Eunice D. Farfan-Garcia, Martiniano Bello, Jose G. Trujillo-Ferrara, Marvin A. Soriano-Ursua
Summary: Levodopa is a cornerstone in Parkinson's disease treatment, mainly by binding on D-2 receptors. Research found that a Dopaboroxazolidone (DPBX) has higher affinity on D2DR than levodopa, with essential interactions with residues in the third and sixth transmembrane domains of the D2DR being crucial for inducing and stabilizing interactions in the active receptor state. Results suggest DPBX's efficacy is similar to that of levodopa in diminishing MPTP-induced parkinsonism, and this beneficial effect is disrupted with prior D2DR antagonist administration.
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Miguel A. Labrador-Espinosa, Michel J. Grothe, Daniel Macias-Garcia, Silvia Jesus, Astrid Adarmes-Gomez, Laura Munoz-Delgado, Paula Fernandez-Rodriguez, Juan Francisco Martin-Rodriguez, Ismael Huertas, David Garcia-Solis, Pablo Mir
Summary: The study found that reductions in DAT levels in the sensorimotor striatal subregion were most pronounced in PD patients who developed LID, providing a potentially sensitive tool for early detection and improved prognosis of this common complication in PD.
CLINICAL NUCLEAR MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Alfonsina Tirozzi, Nicola Modugno, Nicole Piera Palomba, Rosangela Ferese, Alessia Lombardi, Enrica Olivola, Alessandro Gialluisi, Teresa Esposito
Summary: The study found that late PD onset and male gender have a protective effect against LID risk, with disease duration being the most prominent feature influencing LID risk. Therefore, personalized therapeutic protocols are important for PD patients in the future.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Neurosciences
Efthalia Angelopoulou, Yam Nath Paudel, Thomas Julian, Mohd Farooq Shaikh, Christina Piperi
Summary: The exact etiology of Parkinson's disease (PD) is still unknown, and there is no cure for PD. Fyn, a tyrosine phospho-transferase, may play a crucial role in the pathogenesis of PD and levodopa-induced dyskinesia (LID) by regulating key signaling pathways. Therapeutic targeting of Fyn or Fyn-related pathways could represent a novel approach in PD treatment.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Maria Joao Bonifacio, Filipa Sousa, Patricio Soares-da-Silva
Summary: Opicapone, as an adjunctive therapy to levodopa, enhances the effects of levodopa/benserazide combinations in alleviating Parkinson's-like symptoms, leading to improved motor behavior in cynomolgus monkeys, which was later demonstrated in Phase 3 studies in Parkinson's disease patients.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Review
Clinical Neurology
Jorge U. Manez-Miro, Rafael Rodriguez-Rojas, Marta Del Alamo, R. Martinez-Fernandez, Jose A. Obeso
Summary: The authors systematically reviewed the current evidence on subthalamotomy for the treatment of Parkinson's disease, considering focused ultrasound as a minimally invasive, safe, and effective treatment option, especially for asymmetric patients.
EXPERT REVIEW OF NEUROTHERAPEUTICS
(2021)
Review
Immunology
Fanshi Zhang, Mei Liu, Jinmei Tuo, Li Zhang, Jun Zhang, Changyin Yu, Zucai Xu
Summary: This article reviews how neuroinflammation mediates the development of levodopa-induced dyskinesia (LID) through the regulation of NMDA receptors. It also evaluates the potential of common anti-inflammatory drugs and NMDA receptor antagonists to mitigate the development of LID by regulating central neuroinflammation, providing a new theoretical basis for finding new therapeutic targets for LID.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Pharmacology & Pharmacy
Yutaro Ohno, Eri Okita, Mika Kawai-Uchida, Naoko Fukuda, Youji Shoukei, Kazuhiro Soshiroda, Koji Yamada, Tomoyuki Kanda, Shinichi Uchida
Summary: KW-6356 is a novel adenosine A2A receptor antagonist/inverse agonist that has shown significant anti-parkinsonian activity as a monotherapy without inducing dyskinesia in PD patients. In contrast, istradefylline, a first-generation A2A antagonist, has not shown statistically significant efficacy as monotherapy. In this study, KW-6356 was found to have a greater anti-parkinsonian activity and a lower propensity to induce dyskinesia compared to istradefylline in MPTP-treated common marmosets. This suggests that KW-6356 could be a promising non-dopaminergic therapy for PD patients.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Neurosciences
Gunasingh J. Masilamoni, Christopher G. Sinon, Brik A. Kochoian, Arun Singh, Andrew J. McRiner, Liza Leventhal, Stella M. Papa
Summary: This study assessed the effects of a selective PDE9 inhibitor (PDE9i) in a primate model of Parkinson's disease (PD). The results showed that PDE9i enhanced the antiparkinsonian effects of L-DOPA and prolonged its duration of action. This suggests that striatal PDE9 inhibition may be a strategy to improve motor responses to L-DOPA in PD.
Article
Clinical Neurology
Marc Deffains, Marie-Helene Canron, Margaux Teil, Qin Li, Benjamin Dehay, Erwan Bezard, Pierre-Olivier Fernagut
Summary: The study found that chronic dopamine-replacement therapy can significantly ameliorate alpha-synuclein pathology in the non-human primate model of Parkinson's disease. Therefore, patient's dopaminergic medication should be systematically considered when assessing the disease.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Article
Neurosciences
Qianqian Si, Caiting Gan, Heng Zhang, Xingyue Cao, Huimin Sun, Min Wang, Lina Wang, Yongsheng Yuan, Kezhong Zhang
Summary: This study used dynamic functional network connectivity analysis to investigate the neural activity of levodopa-induced dyskinesia in Parkinson's disease. The results suggest that dyskinesia is associated with the dysfunctional inhibition of cognitive executive network on motor loops and excessive excitation of visual network and sensorimotor network.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Clinical Neurology
Imane Frouni, Cynthia Kwan, Stephen G. Nuara, Sebastien Belliveau, Woojin Kang, Adjia Hamadjida, Dominique Bedard, Jim C. Gourdon, Philippe Huot
Summary: The study revealed that positive allosteric modulation of mGlu(2) receptors may be an effective approach for treating dyskinesia, psychosis, and motor fluctuations in Parkinson's disease.
JOURNAL OF NEURAL TRANSMISSION
(2021)
Article
Immunology
Xiao-Xiao Fu, Jin Wang, Hua-Ying Cai, Hong Jiang, Jin-Zhan Jiang, Hao-Hao Chen, Shu Han
Summary: The combination of C16 and Ang-1 treatment alleviates neuroinflammation in PD and promotes the recovery effects of levodopa on neural function.
JOURNAL OF INFLAMMATION RESEARCH
(2022)
Review
Neurosciences
Melanie Bourque, Marc Morissette, Therese Di Paolo
Article
Endocrinology & Metabolism
Laura J. Mosher, Sean C. Godar, Marc Morissette, Kenneth M. McFarlin, Simona Scheggi, Carla Gambarana, Stephen C. Fowler, Therese Di Paolo, Marco Bortolato
PSYCHONEUROENDOCRINOLOGY
(2018)
Article
Anatomy & Morphology
Dave Gagnon, Lara Eid, Dymka Coude, Carl Whissel, Therese Di Paolo, Andre Parent, Martin Parent
FRONTIERS IN NEUROANATOMY
(2018)
Article
Clinical Neurology
Delphine Charvin, Therese Di Paolo, Erwan Bezard, Laurent Gregoire, Akihiro Takano, Guillaume Duvey, Elsa Pioli, Christer Halldin, Rossella Medori, Francois Conquet
MOVEMENT DISORDERS
(2018)
Editorial Material
Neurosciences
F. Gasparini, T. Di Paolo
Article
Endocrinology & Metabolism
Hend Jarras, Melanie Bourque, Andree-Anne Poirier, Marc Morissette, Katherine Coulombe, Therese Di Paolo, Denis Soulet
JOURNAL OF NEUROENDOCRINOLOGY
(2020)
Article
Neurosciences
Jordan Nadeau, Tara Smith, Jerome Lamontagne-Proulx, Melanie Bourque, Sara Al Sweidi, Dushmanthi Jayasinghe, Shawn Ritchie, Therese Di Paolo, Denis Soulet
Article
Immunology
Cynthia Lecours, Marie-Kim St-Pierre, Katherine Picard, Maude Bordeleau, Melanie Bourque, Ifeoluwa Oluleke Awogbindin, Amin Benadjal, Fernando Gonzalez Ibanez, Dave Gagnon, Leo Cantin, Martin Parent, Therese Di Paolo, Marie-Eve Tremblay
BRAIN BEHAVIOR AND IMMUNITY
(2020)
Review
Neurosciences
Ifeoluwa Oluleke Awogbindin, Ismail Ogunbayode Ishola, Marie-Kim St-Pierre, Micael Carrier, Julie C. Savage, Therese Di Paolo, Marie-Eve Tremblay
NEUROSCIENCE LETTERS
(2020)
Article
Neurosciences
Amandine Isenbrandt, Marc Morissette, Melanie Bourque, Jerome Lamontagne-Proulx, Katherine Coulombe, Denis Soulet, Therese Di Paolo
Summary: The study examined the effects of sex hormones on a mouse model of Parkinson's disease and the neuroprotective role of the 5 alpha-reductase inhibitor dutasteride. Results showed sex differences in mice MPTP toxicity and response to dutasteride, with implications of neuroinflammation.
Review
Neurosciences
Ifeoluwa O. Awogbindin, Benneth Ben-Azu, Babatunde A. Olusola, Elizabeth T. Akinluyi, Philip A. Adeniyi, Therese Di Paolo, Marie-Eve Tremblay
Summary: Since December 2019, humanity has been facing the devastating SARS-CoV-2 outbreak, resulting in over 3.1 million deaths globally. SARS-CoV-2 infection may lead to neurological symptoms and potentially cause chronic or permanent changes to neural tissues.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Cell Biology
Marc Morissette, Melanie Bourque, Marie-Eve Tremblay, Therese Di Paolo
Summary: Inflammatory markers were found in the brains of Parkinson's disease patients. The study showed that MPEP reduced the development of L-Dopa-induced dyskinesias (LID) in MPTP-lesioned monkeys and decreased inflammatory markers in the brain. The results demonstrated increased inflammatory markers in the basal ganglia associated with LID and revealed the potential of MPEP in reducing LID and inflammatory response.
Article
Biochemical Research Methods
Valerie Brousseau, Patrick Caron, Jocelyn Trottier, Therese Di Paolo, Piotr Milkiewicz, Olivier Barbier
Summary: This study developed a method for quantification of 24S-hydroxycholesterol and its derivatives in human plasma and validated its clinical applications. The results indicate the accumulation of cerebrosterol and its conjugates in the plasma of cholestatic patients.
JOURNAL OF MASS SPECTROMETRY
(2022)
Article
Pharmacology & Pharmacy
Andree-Anne Poirier, Melissa Cote, Hend Jarras, Nadhir Litim, Jerome Lamontagne-Proulx, Sara Al-Sweidi, Marc Morissette, Asmaa Lachhab, Martin Pelletier, Therese Di Paolo, Denis Soulet
Summary: This study demonstrates that dutasteride can prevent enteric neuronal damage in the MPTP mouse model of Parkinson's disease by anti-inflammatory and mitochondrial effects, suggesting that drug repurposing of dutasteride might be a promising avenue to treat enteric neuroinflammation in early PD.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Melanie Bourque, Laurent Gregoire, Waseema Patel, David Dickens, Ralph Snodgrass, Therese Di Paolo
Summary: N-methyl-D-aspartate (NMDA) receptors have been implicated in L-Dopa-induced dyskinesias (LID) in Parkinson's disease patients. L-4-chlorokynurenine (AV-101) is a pro-drug of 7-chlorokynurenic acid, a specific antagonist of the glycine co-agonist site of NMDA receptors. This study investigated the effects of AV-101 on LID in MPTP-lesioned monkeys and found that it reduced LID and maintained the antiparkinsonian activity of L-Dopa. AV-101 showed comparable antidyskinetic activity to amantadine but without adverse effects.