Article
Neurosciences
Virginie J. Oberto, Jumpei Matsumoto, Marco N. Pompili, Ralitsa Todorova, Francesco Papaleo, Hisao Nishijo, Laurent Venance, Marie Vandecasteele, Sidney I. Wiener
Summary: This study compares the oscillations of different frequencies in dopaminergic neurons and their relationship with behavior. It shows that dopaminergic neurons have stronger activity in the moderate to fast frequency bands and play an important role in operant olfactory and visual discrimination tasks.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Hong Li, Houbo Jiang, Hanqin Li, Li Li, Zhen Yan, Jian Feng
Summary: This study is significant as it uses small-molecule compounds to generate Parkinson's disease-related neurons from human induced pluripotent stem cells, providing valuable insights for PD research and treatment development.
MOLECULAR PSYCHIATRY
(2022)
Article
Multidisciplinary Sciences
Theodoros Tsetsenis, Julia K. Badyna, Julianne A. Wilson, Xiaowen Zhang, Elizabeth N. Krizman, Manivannan Subramaniyan, Kechun Yang, Steven A. Thomas, John A. Dani
Summary: This study identifies a cluster of midbrain dopamine neurons near the hippocampus that send direct projections and play a crucial role in aversive memory formation. The neuromodulation of midbrain dopamine in the hippocampus is sufficient to maintain aversive memory formation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Razan Sheta, Maxime Teixeira, Walid Idi, Marion Pierre, Aurelie de Rus Jacquet, Vincent Emond, Cornelia E. Zorca, Benoit Vanderperre, Thomas M. Durcan, Edward A. Fon, Frederic Calon, Mohamed Chahine, Abid Oueslati
Summary: Using human derived induced pluripotent stem cells (hiPSCs) to differentiate into dopaminergic neurons provides a valuable experimental model for investigating the mechanisms of Parkinson's disease (PD). However, current approaches have limitations such as lengthy protocols and variability in neuron yield. This study presents an improved method that combines neurogenin-2 programming with commercially available midbrain differentiation kits to quickly and efficiently generate mature and functional induced DA neurons. The resulting neurons showed similarities to A9 midbrain neurons and exhibited selective vulnerability to 6-hydroxydopamine, making them a suitable in vitro model for studying PD and screening neuroprotective compounds.
SCIENTIFIC REPORTS
(2022)
Article
Medicine, Research & Experimental
Peibo Xu, Hui He, Qinqin Gao, Yingying Zhou, Ziyan Wu, Xiao Zhang, Linyu Sun, Gang Hu, Qian Guan, Zhiwen You, Xinyue Zhang, Wenping Zheng, Man Xiong, Yuejun Chen
Summary: This study provides insights into the cellular heterogeneity during midbrain dopaminergic (mDA) neuron differentiation and establishes a strategy to generate highly purified donor cells for stable and predictable therapeutic outcomes.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Multidisciplinary Sciences
Federico Miozzo, Luca Stickley, Eva P. Valencia-Alarcon, Michaela Dorcikova, Francesco Petrelli, Damla Tas, Nicolas Loncle, Irina Nikonenko, Peter Bou Dib, Emi Nagoshi
Summary: This study identifies a conserved mechanism by which a transcription factor regulates mitochondrial health in dopaminergic neurons. By studying fruit fly and mouse models, the researchers demonstrate that this transcription factor maintains mitochondrial structure and function during aging, playing a crucial role in neuroprotection.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Jin Yi Han, Eun-Hye Lee, Sang-Mi Kim, Chang-Hwan Park
Summary: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by tremors, bradykinesia, and rigidity. Stem cell-based therapy using astrocytes as a source for dopamine neurons shows potential as a treatment option. By overexpressing certain transcription factors, astrocytes can be directly converted into dopamine neurons and neural progenitor cells (NPCs). This direct conversion strategy may provide a cell therapy approach for neurodegenerative diseases.
BIOMOLECULES & THERAPEUTICS
(2023)
Article
Cell Biology
Jia Shang, Bin Li, Han Fan, Peidi Liu, Wen Zhao, Tao Chen, Pu Chen, Longqiu Yang
Summary: This study investigated the effects of sevoflurane on the midbrain's development using human physiologically-relevant midbrain organoids. The results showed that long-term exposure to sevoflurane could promote premature differentiation of midbrain organoids and inhibit cell proliferation, indicating a potential adverse effect on the midbrain development in fetuses.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Walaa F. Alsanie, Majid Alhomrani, Ahmed Gaber, Hamza Habeeballah, Heba A. Alkhatabi, Raed I. Felimban, Sherin Abdelrahman, Charlotte A. E. Hauser, Adeel G. Chaudhary, Abdulhakeem S. Alamri, Bassem M. Raafat, Abdulwahab Alamri, Sirajudheen Anwar, Khaled A. Alswat, Yusuf S. Althobaiti, Yousif A. Asiri
Summary: This study found that early exposure to pregabalin could interfere with the development of ventral midbrain dopaminergic neurons, which is crucial for clinical consideration of its use during pregnancy.
Article
Physiology
Toshiyuki Fujita, Naoya Aoki, Chihiro Mori, Shouta Serizawa, Fumiko Kihara-Negishi, Koichi J. J. Homma, Shinji Yamaguchi
Summary: The study revealed the reciprocal regulation between dopaminergic and serotonergic neurons in birds, with 5-HTR1A and 5-HTR1B receptors expressed in midbrain dopaminergic nuclei playing a role in the serotonergic regulation of the dopaminergic system. This finding enhances our understanding of the interaction between dopamine and serotonin systems in birds at the molecular level.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Neurosciences
Jackson Brougher, Umaymah Aziz, Nikitha Adari, Muskaan Chaturvedi, Aryela Jules, Iqra Shah, Saba Syed, Catherine A. Thorn
Summary: The study compared the effects of right cervical vagus nerve stimulation (r-VNS) with traditional left VNS (l-VNS) on self-administration behavior and midbrain dopaminergic activation in rats. The results showed that rats stimulated with r-VNS exhibited significantly more lever presses and greater c-Fos expression in dopamine-related brain regions compared to l-VNS, suggesting a preferential activation of the midbrain dopaminergic system by targeting the right cervical nerve.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Diego Sucunza, Alberto J. Rico, Elvira Roda, Maria Collantes, Gloria Gonzalez-Aseguinolaza, Ana I. Rodriguez-Perez, Ivan Penuelas, Alfonso Vazquez, Jose L. Labandeira-Garcia, Vania Broccoli, Jose L. Lanciego
Summary: Mutations in the GBA1 gene are the main genetic risk factor for Parkinson's disease, and enhancing GCase activity can reduce alpha-synuclein burden and prevent dopaminergic cell death. Gene therapy targeting GCase can improve survival of dopaminergic neurons and serve as a disease-modifying treatment for PD and related synucleinopathies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Lydia Hellrung, Matthias Kirschner, James Sulzer, Ronald Sladky, Frank Scharnowski, Marcus Herdener, Philippe N. Tobler
Summary: Analysis of real-time fMRI data suggests that reinforcement learning contributes to successful self-regulation in the dopaminergic midbrain. The study found that successful self-regulation is associated with prefrontal reward sensitivity, decreasing relation between prefrontal activity and midbrain learning signals during neurofeedback training, and increased activity within cognitive control areas during transfer.
COMMUNICATIONS BIOLOGY
(2022)
Article
Neurosciences
Gurvir S. Virdi, Minee L. Choi, James R. Evans, Zhi Yao, Dilan Athauda, Stephanie Strohbuecker, Raja S. Nirujogi, Anna Wernick, Noelia Pelegrina-Hidalgo, Craig Leighton, Rebecca S. Saleeb, Olga Kopach, Haya Alrashidi, Daniela Melandri, Jimena Perez-Lloret, Plamena R. Angelova, Sergiy Sylantyev, Simon Eaton, Simon Heales, Dmitri A. Rusakov, Dario R. Alessi, Tilo Kunath, Mathew H. Horrocks, Andrey Y. Abramov, Rickie Patani, Sonia Gandhi
Summary: Using human-induced pluripotent stem cells, researchers have discovered that protein misfolding leading to intraneuronal oligomer formation is one of the earliest critical events in Parkinson's disease. This leads to cellular stress and ultimately neuronal death.
NPJ PARKINSONS DISEASE
(2022)
Article
Immunology
Fernando Bandeira Sulczewski, Raul A. Maqueda-Alfaro, Marcela Alcantara-Hernandez, Oriana A. Perez, Sanjana Saravanan, Tae Jin Yun, David Seong, Rebeca Arroyo Hornero, Hayley M. Raquer-McKay, Eduardo Esteva, Zachary R. Lanzar, Rebecca A. Leylek, Nicholas M. Adams, Annesa Das, Adeeb H. Rahman, Andres Gottfried-Blackmore, Boris Reizis, Juliana Idoyaga
Summary: This study investigates the role of transitional dendritic cells (tDCs) in antiviral immune responses and reveals their distinct features compared to other dendritic cell subsets. The authors show that tDCs share bone marrow progenitors with plasmacytoid DCs (pDCs) and contribute to the development of ESAM(+) type 2 DCs (DC2s). Unlike other DC subsets, tDCs exhibit characteristics of differentiated DCs, including antigen capture, response to stimuli, and activation of antigen-specific naive T cells. Moreover, viral sensing by tDCs leads to IL-1β secretion and fatal immune pathology. Overall, tDCs are a unique pDC-related subset with a DC2 differentiation potential and a special proinflammatory function during viral infections.
Article
Biochemistry & Molecular Biology
Marlene Louise Quaade, Pratibha Dhumale, Simon Gabriel Comerma Steffensen, Hans Christian Beck, Eva Bang Harvald, Charlotte Harken Jensen, Lars Lund, Ditte Caroline Andersen, Soren Paludan Sheikh
Summary: The study found that diabetes does not appear to limit the effectiveness of autologous adipose stem cell therapy for treating erectile dysfunction (ED). Both diabetic and non-diabetic rats' adipose stem cells showed similar abilities in restoring erectile function and inducing genes related to endothelial function recovery.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Mohammad Dehestani, Hui Liu, Ashwin Ashok Kumar Sreelatha, Claudia Schulte, Vikas Bansal, Thomas Gasser
Summary: This study assessed the predictive utility of PRS models constructed based on SNPs corresponding to two cardinal pathways in Parkinson's disease (PD). The results showed that these pathway PRS significantly predict PD risk, and mitochondrial PRS are significantly associated with later age of onset in PD patients.
MOLECULAR AND CELLULAR NEUROSCIENCE
(2022)
Article
Clinical Neurology
Cloe Domenighetti, Venceslas Douillard, Pierre-Emmanuel Sugier, Ashwin Ashok Kumar Sreelatha, Claudia Schulte, Sandeep Grover, Patrick May, Dheeraj R. Bobbili, Milena Radivojkov-Blagojevic, Peter Lichtner, Andrew B. Singleton, Dena G. Hernandez, Connor Edsall, Pierre-Antoine Gourraud, George D. Mellick, Alexander Zimprich, Walter Pirker, Ekaterina Rogaeva, Anthony E. Lang, Sulev Koks, Pille Taba, Suzanne Lesage, Alexis Brice, Jean-Christophe Corvol, Marie-Christine Chartier-Harlin, Eugenie Mutez, Kathrin Brockmann, Angela B. Deutschlander, Georges M. Hadjigeorgiou, Efthimos Dardiotis, Leonidas Stefanis, Athina Maria Simitsi, Enza Maria Valente, Simona Petrucci, Stefano Duga, Letizia Straniero, Anna Zecchinelli, Gianni Pezzoli, Laura Brighina, Carlo Ferrarese, Grazia Annesi, Andrea Quattrone, Monica Gagliardi, Hirotaka Matsuo, Akiyoshi Nakayama, Nobutaka Hattori, Kenya Nishioka, Sun Ju Chung, Yun Joong Kim, Pierre Kolber, Bart P. C. van de Warrenburg, Bastiaan R. Bloem, Jan Aasly, Mathias Toft, Lasse Pihlstrom, Leonor Correia Guedes, Joaquim J. Ferreira, Soraya Bardien, Jonathan Carr, Eduardo Tolosa, Mario Ezquerra, Pau Pastor, Monica Diez-Fairen, Karin Wirdefeldt, Nancy L. Pedersen, Caroline Ran, Andrea C. Belin, Andreas Puschmann, Emil Ygland Rodstrom, Carl E. Clarke, Karen E. Morrison, Manuela Tan, Dimitri KraincMD, Lena F. Burbulla, Matt J. Farrer, Rejko Kruger, Thomas Gasser, Manu Sharma, Nicolas Vince, Alexis Elbaz
Summary: This study conducted a large-scale independent replication of the interaction between HLA-DRB1 and smoking in Parkinson's disease. The valine at position 11 (V11) in HLA-DRB1 showed the strongest association with PD at the amino acid level. The results suggest an inverse association between genetically predicted smoking initiation and PD, particularly in individuals without the V11 variant. In silico predictions support this interaction pattern by showing the influence of V11 and smoking-induced modifications on binding affinity of alpha-synuclein.
MOVEMENT DISORDERS
(2022)
Article
Medicine, General & Internal
G. Pagano, K. I. Taylor, J. Anzures-Cabrera, M. Marchesi, T. Simuni, K. Marek, R. B. Postuma, N. Pavese, F. Stocchi, J. -P. Azulay, B. Mollenhauer, L. Lopez-Manzanares, D. S. Russell, J. T. Boyd, A. P. Nicholas, M. R. Luquin, R. A. Hauser, T. Gasser, W. Poewe, B. Ricci, A. Boulay, A. Vogt, F. G. Boess, J. Dukart, G. D'Urso, R. Finch, S. Zanigni, A. Monnet, N. Pross, A. Hahn, H. Svoboda, M. Britschgi, F. Lipsmeier, E. Volkova-Volkmar, M. Lindemann, S. Dziadek, S. Holiga, D. Rukina, T. Kustermann, G. A. Kerchner, P. Fontoura, D. Umbricht, R. Doody, T. Nikolcheva, A. Bonni
Summary: The study found that prasinezumab had no meaningful effect on global or imaging measures of Parkinson's disease progression and was associated with infusion reactions.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Multidisciplinary Sciences
Sebastian Schmidt, Malte D. Luecken, Dietrich Truembach, Sina Hembach, Kristina M. Niedermeier, Nicole Wenck, Klaus Pfluegler, Constantin Stautner, Anika Boettcher, Heiko Lickert, Ciro Ramirez-Suastegui, Ruhel Ahmad, Michael J. Ziller, Julia C. Fitzgerald, Viktoria Ruf, Wilma D. J. van de Berg, Allert J. Jonker, Thomas Gasser, Beate Winner, Juergen Winkler, Daniela M. Vogt Weisenhorn, Florian Giesert, Fabian J. Theis, Wolfgang Wurst
Summary: Using single-cell RNA sequencing, the researchers found that neuronal cells from Parkinson's disease patients have altered primary cilia morphology and signaling, suggesting that cilia dysfunction may underlie the pathogenesis of Parkinson's disease.
NATURE COMMUNICATIONS
(2022)
Article
Clinical Neurology
Thomas Gasser
Summary: After years of research and setbacks, gene therapies have achieved undeniable success by directly modifying genetic information on the DNA or RNA level. Both ex vivo strategies, manipulating patient cells outside the body, and in vivo approaches have been successful. In addition to gene supplementation, the use of the CRISPR-Cas9 system for altering nuclear DNA sequences and interfering with the transcriptional process on the RNA level can also be considered as gene therapies in a broad sense.
FORTSCHRITTE DER NEUROLOGIE PSYCHIATRIE
(2023)
Review
Clinical Neurology
Ullrich Wuellner, Per Borghammer, Chi-un Choe, Ilona Csoti, Bjorn Falkenburger, Thomas Gasser, Paul Lingor, Peter Riederer
Summary: The heterogeneity of Parkinson's disease presents challenges for future research and therapeutic design. Various pathophysiological concepts and mechanisms, including alpha-synuclein misfolding, oxidative stress, and microbial agents, may contribute to the development of PD. The unresolved heterogeneity of PD has hindered previous clinical trials, highlighting the need for personalized therapeutic approaches.
JOURNAL OF NEURAL TRANSMISSION
(2023)
Review
Clinical Neurology
Thomas Gasser
Summary: The identification of disease-causing mutations or strong risk factors for Parkinson's disease in specific genes has led to a better understanding of disease pathogenesis. Many gene and mutation-specific targeted disease-modifying treatments are being developed and studied. Therefore, it is important to raise awareness and offer genetic testing to patients considering innovative trials.
JOURNAL OF NEURAL TRANSMISSION
(2023)
Article
Clinical Neurology
Pierre-Emmanuel Sugier, Elise A. Lucotte, Cloe Domenighetti, Matthew H. Law, Mark M. Iles, Kevin Brown, Christopher Amos, James D. McKay, Rayjean J. Hung, Mojgan Karimi, Delphine Bacq-Daian, Anne Boland-Auge, Robert Olaso, Jean-francois Deleuze, Fabienne Lesueur, Evgenia Ostroumova, Ausrele Kesminiene, Florent de Vathaire, Pascal Guenel, Ashwin Ashok Kumar Sreelatha, Claudia Schulte, Sandeep Grover, Patrick May, Dheeraj R. Bobbili, Milena Radivojkov-Blagojevic, Peter Lichtner, Andrew B. Singleton, Dena G. Hernandez, Connor Edsall, George D. Mellick, Alexander Zimprich, Walter Pirker, Ekaterina Rogaeva, Anthony E. Lang, Sulev Koks, Pille Taba, Suzanne Lesage, Alexis Brice, Jean-Christophe Corvol, Marie-Christine Chartier-Harlin, Eugenie Mutez, Kathrin Brockmann, Angela B. Deutschlaender, Georges M. Hadjigeorgiou, Efthimios Dardiotis, Leonidas Stefanis, Athina Maria Simitsi, Enza Maria Valente, Simona Petrucci, Letizia Straniero, Anna Zecchinelli, Gianni Pezzoli, Laura Brighina, Carlo Ferrarese, Grazia Annesi, Andrea Quattrone, Monica Gagliardi, Hirotaka Matsuo, Akiyoshi Nakayama, Nobutaka Hattori, Kenya Nishioka, Sun Ju Chung, Yun Joong Kim, Pierre Kolber, Bart P. C. van de Warrenburg, Bastiaan R. Bloem, Jan Aasly, Mathias Toft, Lasse Pihlstrom, Leonor Correia Guedes, Joaquim J. Ferreira, Soraya Bardien, Jonathan Carr, Eduardo Tolosa, Mario Ezquerra, Pau Pastor, Monica Diez-Fairen, Karin Wirdefeldt, Nancy Pedersen, Caroline Ran, Andrea C. Belin, Andreas Puschmann, Emil Ygland Roedstroem, Carl E. Clarke, Karen E. Morrison, Manuela Tan, Dimitri Krainc, Lena F. Burbulla, Matt J. Farrer, Rejko Kruger, Thomas Gasser, Manu Sharma, Therese Truong, Alexis Elbaz
Summary: By using genome-wide association studies, this study found that Parkinson's disease (PD) is genetically correlated with melanoma and prostate cancer, while it is inversely correlated with ovarian cancer. These findings suggest that pleiotropic genes contribute to the association between PD and specific cancers.
MOVEMENT DISORDERS
(2023)
Letter
Clinical Neurology
Christos Koros, Kathrin Brockmann, Athina-Maria Simitsi, Anastasia Bougea, Hui Liu, Ann-Kathrin Hauser, Claudia Schulte, Stefanie Lerche, Ioanna Pachi, Nikolaos Papagiannakis, Roubina Antonelou, Athina Zahou, Isabel Wurster, Efthymia Efthymiopoulou, Ion Beratis, Matina Maniati, Marina Moraitou, Helen Michelakakis, Georgios Paraskevas, Sokratis G. Papageorgiou, Constantin Potagas, Dimitra Papadimitriou, Maria Bozi, Maria Stamelou, Thomas Gasser, Leonidas Stefanis
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Nir Giladi, Roy N. Alcalay, Gary Cutter, Thomas Gasser, Tanya Gurevich, Guenter U. Hoeglinger, Kenneth Marek, Claudio Pacchetti, Anthony H. Schapira, Clemens R. Scherzer, Tanya Simuni, Pascal Minini, S. Pablo Sardi, M. Judith Peterschmitt
Summary: The safety, efficacy, and target engagement of venglustat in early-stage Parkinson's disease patients with GBA1 variants were assessed. The study showed that venglustat had a satisfactory safety profile but did not show beneficial treatment effect compared with placebo. These findings suggest that glucosylceramide synthase inhibition with venglustat may not be a viable therapeutic approach for GBA1-associated Parkinson's disease.
Letter
Clinical Neurology
Christos Koros, Kathrin Brockmann, Athina-Maria Simitsi, Anastasia Bougea, Hui Liu, Ann-Kathrin Hauser, Claudia Schulte, Stefanie Lerche, Ioanna Pachi, Nikolaos Papagiannakis, Roubina Antonelou, Athina Zahou, Isabel Wurster, Efthymia Efthymiopoulou, Ion Beratis, Matina Maniati, Marina Moraitou, Helen Michelakakis, Georgios Paraskevas, Sokratis G. Papageorgiou, Constantin Potagas, Dimitra Papadimitriou, Maria Bozi, Maria Stamelou, Thomas Gasser, Leonidas Stefanis
MOVEMENT DISORDERS
(2023)
Article
Geriatrics & Gerontology
Daniela Renftle, Sara Becker, Kathrin Brockmann, Thomas Gasser, Katja Michaelis, Susanne Solbrig, Patricia Sulzer, Andreas Johnen, Inga Liepelt-Scarfone
Summary: This study evaluated the psychometric properties and validity of the Dementia Apraxia Test (DATE) in patients with Parkinson's disease. The results showed that DATE scores were associated with cognition and daily living function, but were confounded by motor impairment and age.
DEMENTIA AND GERIATRIC COGNITIVE DISORDERS
(2022)
Meeting Abstract
Clinical Neurology
S. Grover, E. Wacker, A. Kumar-Sreelatha, A. Elbaz, R. Kruger, T. Gasser, D. Ellinghaus, M. Sharma
MOVEMENT DISORDERS
(2022)
Meeting Abstract
Clinical Neurology
S. Grover, A. Kumar-Sreelatha, Z. Landoulsi, P. May, D. Bobbili, C. Domenighetti, C. Schulte, P. E. Sugier, A. Elbaz, R. Kruger, T. Gasser, M. Sharma
MOVEMENT DISORDERS
(2022)