Review
Cell Biology
Jen-Hsiang T. Hsiao, Onur Tanglay, Anne A. Li, Aysha Y. G. Strobbe, Woojin Scott Kim, Glenda M. Halliday, YuHong Fu
Summary: Multiple system atrophy (MSA) is a debilitating movement disorder with unknown etiology. It presents with characteristic parkinsonism and/or cerebellar dysfunction due to deterioration in specific brain regions. The early pathological events and development mechanisms of MSA are reviewed, focusing on the involvement of oligodendrocyte lineage cells and alpha-synuclein. This understanding will guide future research in MSA.
Article
Chemistry, Multidisciplinary
An Cheng, Wenbin Jia, David I. Finkelstein, Nadia Stefanova, Haoyang Wang, Takuya Sasaki, Ichiro Kawahata, Kohji Fukunaga
Summary: The specific inhibitor MF6 can reduce α-Syn aggregation, improve cell viability, motor function, and reduce oxidative stress and inflammation levels. It also improves cerebellar function and neuron morphology through regulating endocytosis, showing potential for the treatment of multiple system atrophy (MSA).
ACTA PHARMACOLOGICA SINICA
(2023)
Review
Biochemistry & Molecular Biology
Kurt A. Jellinger, Gregor K. Wenning, Nadia Stefanova
Summary: Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disease with a complex clinical presentation. It shares molecular similarities with Parkinson's disease but presents unique pathological features. The debate over whether it should be classified as a prion disease or its potential human transmission remains unresolved.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Sara A. M. Holec, Jisoo Lee, Abby Oehler, Felicia K. Ooi, Daniel A. Mordes, Steven H. Olson, Stanley B. Prusiner, Amanda L. Woerman
Summary: This study demonstrates that MSA prions can transmit neurological disease to mice expressing wild-type SNCA in a sex-dependent manner. The transmission of MSA prions shows distinct biological activities compared to the transmission of WT preformed fibrils.
ACTA NEUROPATHOLOGICA
(2022)
Article
Clinical Neurology
Teresa Torre-Muruzabal, Anke van der Perren, Audrey Coens, Geraldine Gelders, Anna Barber Janer, Sara Camacho-Garcia, Therese Klingstedt, Peter Nilsson, Nadia Stefanova, Ronald Melki, Veerle Baekelandt, Wouter Peelaerts
Summary: This study found that the progression of multiple system atrophy is influenced by different types of alpha Syn strains. Alpha Syn strains impact disease progression through oligodendroglial, neurotoxic, and immune-related mechanisms, leading to neurodegeneration and brain atrophy. The activation of microglial cells is associated with the structural features of alpha Syn strains.
Article
Clinical Neurology
Margaux Teil, Sandra Dovero, Mathieu Bourdenx, Marie-Laure Arotcarena, Sandrine Camus, Gregory Porras, Marie-Laure Thiolat, Ines Trigo-Damas, Celine Perier, Cristina Estrada, Nuria Garcia-Carrillo, Michele Morari, Wassilios G. Meissner, Maria Trinidad Herrero, Miquel Vila, Jose A. Obeso, Erwan Bezard, Benjamin Dehay
Summary: Synucleinopathies, including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, are characterized by the deposit of alpha-synuclein aggregates in neurons and glial cells. A study found that inoculating brain fractions containing glial cytoplasmic inclusions from multiple system atrophy patients into non-human primates resulted in neurodegeneration, oligodendrocyte loss, demyelination, neuroinflammation and alpha-synuclein pathology. These findings suggest the potential use of this experimental model for multiple system atrophy research and therapy development.
Article
Clinical Neurology
An Cheng, Ichiro Kawahata, Yifei Wang, Wenbin Jia, Haoyang Wang, Tomoki Sekimori, Yi Chen, Hiroyoshi Suzuki, Atsushi Takeda, Nadia Stefanova, David Finkelstein, Wenbo Ma, Min Chen, Takuya Sasaki, Kohji Fukunaga
Summary: Multiple system atrophy (MSA) is a neurodegenerative disease characterized by accumulation of misfolded a-synuclein (aSyn) and myelin disruption. This study identified epsin-2 as a potential regulator of aSyn propagation in MSA brains, suggesting epsin-2 as a novel therapeutic target for MSA.
Article
Clinical Neurology
Yasuo Miki, Kunikazu Tanji, Kana Shinnai, Makoto T. Tanaka, Firat Altay, Sandrine C. Foti, Catherine Strand, Takanori Sasaki, Tomoya Kon, Shuji Shimoyama, Tomonori Furukawa, Haruo Nishijima, Hiromi Yamazaki, Yasmine T. Asi, Conceicao Bettencourt, Zane Jaunmuktane, Mari Tada, Fumiaki Mori, Hiroki Mizukami, Masahiko Tomiyama, Hilal A. Lashuel, Tammaryn Lashley, Akiyoshi Kakita, Helen Ling, Andrew J. Lees, Janice L. Holton, Thomas T. Warner, Koichi Wakabayashi
Summary: This study investigated how abnormal alpha-synuclein in the hippocampus leads to memory impairment in multiple system atrophy (MSA). The results suggest that increased alpha-synuclein oligomers may be a pathological cause of memory impairment in MSA.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Article
Clinical Neurology
Takashi Ando, Yuichi Riku, Akio Akagi, Hiroaki Miyahara, Mitsuaki Hirano, Toshimasa Ikeda, Hiroyuki Yabata, Ryuichi Koizumi, Chisato Oba, Saori Morozumi, Keizo Yasui, Atsuko Goto, Taiji Katayama, Satoko Sakakibara, Ikuko Aiba, Motoko Sakai, Masaaki Konagaya, Keiko Mori, Yasuhiro Ito, Hiroyuki Yuasa, Masayo Nomura, Kristine Joyce L. Porto, Jun Mitsui, Shoji Tsuji, Maya Mimuro, Yoshio Hashizume, Masahisa Katsuno, Yasushi Iwasaki, Mari Yoshida
Summary: In this study, MSA patients with prominent hippocampal involvement showed specific demographic and clinical characteristics. The severe hippocampal pathology seen in these patients suggests a potential pathological variant of MSA characterized by neuronal alpha-synucleinopathy.
Article
Neurosciences
Ivan Martinez-Valbuena, Naomi P. Visanji, Ain Kim, Heather H. C. Lau, Raphaella W. L. So, Sohaila Alshimemeri, Andrew Gao, Michael A. Seidman, Maria R. Luquin, Joel C. Watts, Anthony E. Lang, Gabor G. Kovacs
Summary: This study revealed significant differences in the seeding activity of alpha-synuclein in the brains of patients with Multiple System Atrophy (MSA), as well as regional variations within individual brains. These findings provide important experimental groundwork for future subclassification and rapid diagnostic assays for MSA.
TRANSLATIONAL NEURODEGENERATION
(2022)
Article
Biochemistry & Molecular Biology
Francesco De Nuccio, Marianna Kashyrina, Francesca Serinelli, Florent Laferriere, Dario Domenico Lofrumento, Francesca De Giorgi, Francois Ichas
Summary: alpha-Synucleinopathies are neurodegenerative disorders characterized by the accumulation of insoluble alpha-Synuclein fibrils. These fibrils can form Lewy bodies in somata and Lewy neurites in neuronal processes. In multiple system atrophy, alpha-Synuclein aggregates are found in mature oligodendrocytes, but the origin of these aggregates is still unknown.
Review
Biochemistry & Molecular Biology
Chisato Kinoshita, Noriko Kubota, Koji Aoyama
Summary: Multiple system atrophy is a rare neurodegenerative disease that is characterized by oxidative stress, glutathione deficiency, and dysregulation of miRNA. These factors are closely related to the pathology of MSA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
David J. Marmion, Angela A. Rutkowski, Diptaman Chatterjee, Benjamin M. Hiller, Milton H. Werner, Erwan Bezard, Deniz Kirik, Thomas McCown, Steven J. Gray, Jeffrey H. Kordower
Summary: Multiple system atrophy (MSA) is a progressive neurodegenerative disease with unclear pathogenesis. Studies using large animal models have successfully reproduced some pathological features of the disease.
NEUROBIOLOGY OF DISEASE
(2021)
Review
Clinical Neurology
Nadia Stefanova
Summary: Multiple System Atrophy (MSA) is a rare neurodegenerative disorder with unclear etiology, rapid progression, and high mortality. It shares similar neuropathology with Parkinson's disease but has specific features. Currently, there is no efficient therapy for MSA, making the development of experimental models crucial for understanding the disease mechanisms and screening potential therapies. The PLP-α-syn mouse model is a promising model that mimics the motor and non-motor features of MSA, providing insights into the pathology.
Review
Clinical Neurology
Nadia Stefanova
Summary: Multiple system atrophy is a rare neurodegenerative disorder with unclear etiology and no efficient therapy. The development of experimental models is crucial for understanding the disease mechanisms and finding potential treatments.
Review
Clinical Neurology
Ana Marques, Franck Durif, Pierre-Olivier Fernagut
JOURNAL OF NEURAL TRANSMISSION
(2018)
Article
Neurosciences
Miguel Lopez-Cuina, Pierre-Olivier Fernagut, Marie-Helene Canron, Anne Vital, Beatrice Lannes, Andre Maues De Paula, Nathalie Streichenberger, Dominique Guehl, Philippe Damier, Alexandre Eusebio, Jean-Luc Houeto, Francois Tison, Christine Tranchant, Francois Viallet, Tatiana Witjas, Stephane Thobois, Wassilios G. Meissner
NEUROBIOLOGY OF DISEASE
(2018)
Review
Clinical Neurology
Marcello Solinas, Pauline Belujon, Pierre Olivier Fernagut, Mohamed Jaber, Nathalie Thiriet
JOURNAL OF NEURAL TRANSMISSION
(2019)
Editorial Material
Clinical Neurology
Pierre-Olivier Fernagut
MOVEMENT DISORDERS
(2019)
Review
Clinical Neurology
Wassilios G. Meissner, Pierre-Olivier Fernagut, Benjamin Dehay, Patrice Peran, Anne Pavy-Le Traon, Alexandra Foubert-Samier, Miguel Lopez Cuina, Erwan Bezard, Francois Tison, Olivier Rascol
MOVEMENT DISORDERS
(2019)
Article
Clinical Neurology
Miguel Lopez-Cuina, Paul A. Guerin, Marie-Helene Canron, Anna Delamarre, Benjamin Dehay, Erwan Bezard, Wassilios G. Meissner, Pierre-Olivier Fernagut
MOVEMENT DISORDERS
(2020)
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
Multidisciplinary Sciences
Elva Fridjonsdottir, Reza Shariatgorji, Anna Nilsson, Theodosia Vallianatou, Luke R. Odell, Luke S. Schembri, Per Svenningsson, Pierre-Olivier Fernagut, Alan R. Crossman, Erwan Bezard, Per E. Andren
Summary: The L-DOPA treatment for Parkinson's disease can lead to dyskinesias, which is associated with a dysregulation of dopamine metabolism throughout the brain, particularly in extrastriatal regions. In these areas, dopamine levels are closely correlated with L-DOPA levels.
Article
Clinical Neurology
Willy-Paul Westphal, Christophe Rault, Rene Robert, Stephanie Ragot, Jean-Philippe Neau, Pierre-Olivier Fernagut, Xavier Drouot
Summary: Sleep deprivation impairs vagal tone adaptation during inspiratory effort in healthy individuals, decreasing inspiratory endurance. The lack of vagal tonal response to inspiratory load under sleep deprivation results in higher heart rate and reduced inspiratory endurance during the trial.
Article
Clinical Neurology
Fares Bassil, Anna Delamarre, Marie-Helene Canron, Nathalie Dutheil, Anne Vital, Marie-Laure Negrier-Leibreich, Erwan Bezard, Pierre-Olivier Fernagut, Wassilios G. Meissner
Summary: The study found higher IRS-1pS312 expression in both PD patients and a preclinical rat model, indicating brain insulin resistance in PD and supporting the repurposing of anti-diabetic drugs for PD treatment.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Review
Neurosciences
Hendrik Theis, Catharina Probst, Pierre-Olivier Fernagut, Thilo van Eimeren
Summary: In Parkinson's disease, impulse-control disorders may occur during dopamine-replacement therapy due to differences in the layout of the dopamine reinforcement system and alterations in the dopaminergic system. The vulnerability-stress model suggests that a relative reduction of dopaminergic projections to the ventral striatum and concomitant sensitization of postsynaptic neurons play a role in predisposing individuals to these disorders. This model may provide insights into both impulse-control disorders and addictions in the general population.
NPJ PARKINSONS DISEASE
(2021)
Article
Clinical Neurology
Miguel Lopez-Cuina, Paul Guerin, Nathalie Dutheil, Christelle Martin, Thierry Leste Lasserre, Pierre-Olivier Fernagut, Wassilios G. Meissner, Erwan Bezard
Summary: This study demonstrates that lowering brain GRK2 levels through delivery of a GRK2-specific miRNA can reverse central nervous system insulin resistance and provide neuroprotection in a mouse model of multiple system atrophy. These findings suggest that GRK2 may be a potential therapeutic target for the treatment of MSA.
MOVEMENT DISORDERS
(2023)
Article
Neurosciences
Melina Decourt, Eric Balado, Maureen Francheteau, Marcello Solinas, Marianne Benoit-Marand, Pierre-Olivier Fernagut
Summary: Subtle cognitive impairment can occur early in the course of Parkinson's disease (PD) and may manifest under different forms of executive dysfunction. The precise contribution of nigrostriatal dopaminergic neurodegeneration to these non-motor features of the disease is poorly known. This study investigated the contributions of nigrostriatal degeneration and chronic treatment with the dopamine D3-preferring agonist pramipexole on behavioral flexibility in a rat model of PD.
NPJ PARKINSONS DISEASE
(2023)
Article
Medicine, Research & Experimental
David Mallet, Thibault Dufourd, Melina Decourt, Carole Carcenac, Paola Bossu, Laure Verlin, Pierre-Olivier Fernagut, Marianne Benoit-Marand, Gianfranco Spalletta, Emmanuel L. Barbier, Sebastien Carnicella, Veronique Sgambato, Florence Fauvelle, Sabrina Boulet
Summary: By studying metabolic markers in animal models and PD patients, we identified a promising composite biomarker that can accurately diagnose early-stage PD and predict its development before motor symptoms appear.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Medicine, Research & Experimental
Marie-Laure Arotcarena, Mathieu Bourdenx, Nathalie Dutheil, Marie-Laure Thiolat, Evelyne Doudnikoff, Sandra Dovero, Andrea Ballabio, Pierre-Olivier Fernagut, Wassilios G. Meissner, Erwan Bezard, Benjamin Dehay
Article
Neurosciences
Yang He, Jun Tang, Meng Zhang, Junjie Ying, Dezhi Mu
Summary: This study investigated the protective effects and mechanisms of human placenta derived mesenchymal stem cells (hPMSCs) transplantation in a rat model of hypoxic-ischemic encephalopathy (HIE). The results showed that hPMSCs transplantation reduced apoptosis and improved long-term neurological prognosis. Furthermore, the downregulation of Sema 3A/NRP-1 expression and activation of the PI3K/Akt/mTOR signaling pathway played a key role in the protective effects of hPMSCs.
Article
Neurosciences
Emily L. Isenstein, Edward G. Freedman, Jiayi Xu, Ian A. DeAndrea-Lazarus, John J. Foxe
Summary: This study evaluated electrophysiological discrimination of parametric somatosensory stimuli in healthy young adults to understand how the brain processes the duration of tactile information. The results showed that participants did not electrophysiologically discriminate between 100 and 115 ms, but they exhibited distinct electrophysiological responses when the deviant stimuli were 130, 145, and 160 ms. These findings contribute to a better understanding of tactile sensitivity in different clinical conditions.
Article
Neurosciences
Juliana R. Souza, Ludmila Lima-Silveira, Daniela Accorsi-Mendonca, Benedito H. Machado
Summary: This study demonstrates that A2A receptors play a crucial role in modulating synaptic transmission in the NTS neurons and are required for the enhancement of glutamatergic transmission observed under short-term sustained hypoxia conditions.
Article
Neurosciences
Miki Hashizume, Rina Ito, Rie Suge, Yasushi Hojo, Gen Murakami, Takayuki Murakoshi
Summary: The basolateral amygdaloid complex (BLA) is closely involved in the formation of emotional memories, including both aversive memory and contextual fear memory. Acute sleep deprivation (SD) disrupts the acquisition of tone-associated fear memory in juvenile rats, but has no significant effect on contextual fear memory. Slow network oscillation in the amygdala contributes to the formation of amygdala-dependent fear memory in relation to sleep.
Article
Neurosciences
Qunxian Wang, Shipeng Guo, Dongjie Hu, Xiangjun Dong, Zijun Meng, Yanshuang Jiang, Zijuan Feng, Weihui Zhou, Weihong Song
Summary: GSDME plays a crucial role in the pathogenesis of Alzheimer's disease by regulating the switch from apoptosis to pyroptosis and participating in neuroinflammatory response. Knockdown of GSDME has been shown to improve cognitive impairments, indicating that GSDME could be a therapeutic target for Alzheimer's disease.
