Article
Immunology
Jinyuan Luoqian, Wenyong Yang, Xulong Ding, Qing-zhang Tuo, Zheng Xiang, Zhaoyue Zheng, Yu-jie Guo, Li Li, Pengbo Guan, Scott Ayton, Biao Dong, Huiyuan Zhang, Hongbo Hu, Peng Lei
Summary: This study discovered a potential role of ferroptosis, an iron-dependent regulated cell death mechanism, in multiple sclerosis (MS), and proposed the possibility of targeting ferroptosis for MS treatment.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Immunology
Michael Linzey, Krista DiSano, Nora Welsh, Andrew Pachner, Francesca Gilli
Summary: The study found significantly increased expression of complement factors in two clinically distinct mouse models of MS, with the classical complement pathway associated with pathogenesis in the progressive disease and the alternative pathway related to a worse outcome in the relapsing form. Understanding the roles of the complement system in MS is critical for the development of targeted therapies in the future.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Neurosciences
Tal Ganz, Omri Zveik, Nina Fainstein, Marva Lachish, Ariel Rechtman, Lihi Sofer, Livnat Brill, Tamir Ben-Hur, Adi Vaknin-Dembinsky
Summary: Pushing OPC into differentiation program may help overcome remyelination failure, but creating a permissive environment for OPC activation, migration, and differentiation is also crucial.
Review
Neurosciences
Francesca Gilli, Antonia Ceccarelli
Summary: Given the complexity of multiple sclerosis (MS) and the limitations of animal models, this review focuses on the use of three major types of murine models (EAE, viral models, and toxic models) to study key aspects of MS. The combination of MRI technologies with other experimental strategies allows for noninvasive longitudinal studies and provides complementary information on MS pathology. The review also introduces advanced techniques and references specialized literature.
JOURNAL OF NEUROSCIENCE RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Peter G. E. Kennedy, Woro George, Xiaoli Yu
Summary: The etiology of multiple sclerosis (MS) remains unclear. There is controversy regarding whether neural cell apoptosis is the key event initiating and driving the pathological cascade, and the role of inflammation-independent and cell autonomous neuronal processes in axonal damage needs further exploration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Sergey Kalinin, Douglas L. Feinstein
Summary: This study found that conditional knockout of astrocyte-derived LCN2 in experimental autoimmune encephalomyelitis (EAE) delayed clinical scores and reduced astrocyte GFAP expression. Furthermore, decreased expression of oligodendrocyte proteolipid protein and transcription factor Olig2 was observed, suggesting that astrocyte LCN2 contributes to early events and reduces damage to mature oligodendrocytes in EAE.
NEUROSCIENCE LETTERS
(2023)
Review
Cell Biology
Maria Concetta Geloso, Nadia D'Ambrosi
Summary: Microglia can rapidly respond to environmental changes and play a role in shaping neuronal wiring. They regulate the elimination of weaker synapses, actively participating in modulating neuronal function. Synaptic dysfunction may be an early and independent event in the neurodegenerative process associated with diseases like multiple sclerosis.
Article
Multidisciplinary Sciences
Insha Zahoor, Hamid Suhail, Indrani Datta, Mohammad Ejaz Ahmed, Laila M. Poisson, Jeffrey Waters, Faraz Rashid, Rui Bin, Jaspreet Singh, Mirela Cerghet, Ashok Kumar, Md Nasrul Hoda, Ramandeep Rattan, Ashutosh K. Mangalam, Shailendra Giri
Summary: Metabolic aberrations were found to impact the pathogenesis of relapsing-remitting multiple sclerosis, with changes in multiple metabolic pathways identified in patient samples. Enhanced glycolysis in immune cells of MS patients was observed, and treatment with a glycolytic inhibitor showed promising effects in ameliorating disease progression by promoting an antiinflammatory phenotype. This study highlights the potential of blood-based metabolomic approaches in identifying therapeutic targets for developing new treatment strategies for multiple sclerosis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Bridget Shafit-Zagardo, Simone Sidoli, James E. Goldman, Juwen C. DuBois, John R. Corboy, Stephen M. Strittmatter, Hillary Guzik, Ukuemi Edema, Anita G. Arackal, Yair M. Botbol, Emilio Merheb, Rashed M. Nagra, Sarah Graff
Summary: During inflammatory, demyelinating diseases such as multiple sclerosis (MS), inflammation and axonal damage are prevalent early in the course. This study found that the insoluble protein TMEM106B, normally lysosome-associated, is insoluble in MS plaques relative to normal-appearing white matter from individuals with Alzheimer's disease and non-neurologic controls. Hypomorphic mice with a reduction in TMEM106B have increased axonal damage and lipid droplet accumulation in the spinal cord following experimental autoimmune encephalomyelitis.
Article
Multidisciplinary Sciences
Davy Vanhoutte, Tobias G. Schips, Alexander Vo, Kelly M. Grimes, Tanya A. Baldwin, Matthew J. Brody, Federica Accornero, Michelle A. Sargent, Jeffery D. Molkentin
Summary: The Thbs family of proteins, particularly Thbs1, plays a critical role in regulating adult cardiomyocyte size in the stressed heart through activation of PERK-eIF2 alpha -ATF4-induced autophagy.
NATURE COMMUNICATIONS
(2021)
Review
Neurosciences
Morgan W. Psenicka, Brandon C. Smith, Rachel A. Tinkey, Jessica L. Williams
Summary: Neurodegenerative diseases often involve inflammation, and multiple sclerosis (MS) is a complex interplay between inflammation and neurodegeneration. Oligodendrocyte precursor cells (OPCs) play an active role in promoting neuroinflammation and neurodegeneration in MS, in addition to being a target of autoimmune pathology.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Immunology
Jin Wang, Kellie Brown, Caroline Danehy, Emmanuel Merigeon, Stephen Goralski, Samuel Rice, Kwame Torgbe, Fridtjof Thomas, David Block, Henrik Olsen, Scott E. Strome, Elizabeth A. Fitzpatrick
Summary: This study tested the efficacy of a recombinant Fc multimer (M019) in treating multiple sclerosis using a murine model. The results showed that M019 effectively reduced clinical symptoms, inhibited immune cell infiltration into the central nervous system, and interacted with Fc gamma R bearing-monocytes.
FRONTIERS IN IMMUNOLOGY
(2023)
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.
Review
Biochemistry & Molecular Biology
Zhicheng Liu, Jeffrey Waters, Bin Rui
Summary: This review provides an overview of the applications of metabolomics in studying perturbed metabolic pathways in multiple sclerosis (MS) and its potential for personalized treatments. Metabolic alterations associated with MS progression can be revealed through metabolomics, and informative variations of metabolites can serve as potential biomarkers for understanding MS pathogenesis, predicting disease progression, and estimating drug effects.
BIOMEDICAL JOURNAL
(2022)
Article
Neurosciences
Berta Alcover-Sanchez, Gonzalo Garcia-Martin, Juan Escudero-Ramirez, Carolina Gonzalez-Riano, Paz Lorenzo, Alfredo Gimenez-Cassina, Laura Formentini, Pedro de la Villa-Polo, Marta P. Pereira, Francisco Wandosell, Beatriz Cubelos
Summary: Fast synaptic transmission in vertebrates relies on myelin, which is essential for insulation and metabolic support. Disruption of myelination, as seen in R-Ras1(-/-) and/or R-Ras2(-/-) mice, can lead to increased levels of reactive oxygen species and aberrant myelinated axons, mimicking characteristics of myelin diseases such as multiple sclerosis. Loss of R-Ras function may reproduce key features of hypomyelinating diseases, suggesting that R-Ras1(-/-) and R-Ras2(-/-) neurological models are valuable for studying these myelin pathologies.
Article
Neurosciences
Zhixin Lei, Yuan Yue, Sarrabeth Stone, Shuangchan Wu, Wensheng Lin
JOURNAL OF NEUROSCIENCE
(2020)
Article
Neurosciences
Shuangchan Wu, Sarrabeth Stone, Yuan Yue, Wensheng Lin
Summary: The integrated UPR and ERAD mechanisms are essential for maintaining ER homeostasis and the viability of mature SCs in the peripheral nervous system. Sel1L deficiency in SCs leads to ER stress and UPR activation, impacting mature SCs but not actively myelinating SCs during development.
Article
Biochemistry & Molecular Biology
Milos Stanojlovic, Jean Pierre Pallais, Catherine M. Kotz
Summary: This study indicates that Parkinson's disease is associated with damage to orexin neurons and behavioral impairments. By using the A53T mouse model of Parkinson's, measuring various parameters, and evaluating neuronal disruptions, the researchers further confirmed this idea.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Hannah Bender, Simone A. Fietz, Franziska Richter, Milos Stanojlovic
Summary: The study in Thy1-aSyn mice reveals the impact of alpha-synuclein pathology on adult neurogenesis, showing an increase in early stage progenitors but no change in late stage progenitors and neurons. Increased astroglia marker in the hippocampus of transgenic mice was not specific to regions of adult neurogenesis, suggesting no commitment of additional early stage progenitors to astroglia lineage.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Julian Meyer Berger, Gerard Karsenty
Summary: Bone biology has been exploring the impact of molecules on cell differentiation and bone function, and it has been discovered that bone has functions beyond bone formation. The bone-derived hormone osteocalcin affects multiple organs and physiological processes, and the classical and endocrine functions of bone help define a new functional identity for this tissue.
Editorial Material
Immunology
Gerard Karsenty
Summary: This study demonstrates that a prevalent hematological condition can lead to osteoporosis through a remarkable alliance of human and mouse genetics, highlighting the importance of the relationship between bone and its marrow.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Editorial Material
Cell Biology
Jana Bonsberger, Franziska Richter, Milos Stanojlovic
NEURAL REGENERATION RESEARCH
(2022)
Article
Neurosciences
Eileen Ruth S. Torres, Milos Stanojlovic, Moriel Zelikowsky, Jana Bonsberger, Sindalana Hean, Caitlin Mulligan, Leonie Baldauf, Sheila Fleming, Eliezer Masliah, Marie-Francoise Chesselet, Michael S. Fanselow, Franziska Richter
Summary: Parkinson's disease is characterized by early non-motor symptoms such as increased fear and anxiety, potentially linked to abnormal accumulation of alpha-synuclein and pathology in the amygdala. This study in transgenic mice suggests that alpha-synuclein overexpression may lead to enhanced fear processing through amygdala dysfunction, providing insight into potential therapeutic strategies.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Agriculture, Dairy & Animal Science
Anne Kalies, Johannes Baumgartner, Martin Beyerbach, Milos Stanojlovic, Tobias Scholz, Franziska Richter, Alexandra von Altrock, Isabel Hennig-Pauka
Summary: The study found that pigs with access to a straw-filled interactive rooting tower had fewer and less severe tail lesions, and engaged in more tower manipulation. However, the interactive tower alone was not sufficient to prevent tail biting outbreaks in pigs with intact tails. Early detection of biting pigs was identified as a high priority in preventing tail biting outbreaks.
Article
Neurosciences
Shuangchan Wu, Wensheng Lin
Summary: Endoplasmic reticulum associated degradation (ERAD) is responsible for recognizing and degrading unfolded or misfolded proteins in the ER. Sel1L is essential for the ERAD activity and its knockout in mature myelinating cells caused myelin abnormalities in the adult CNS and PNS. The knockout impaired ERAD, leading to ER stress and UPR activation, and suppressed myelin protein translation, resulting in myelin thinning and demyelination in the adult CNS and PNS.
Review
Clinical Neurology
Franziska Richter, Milos Stanojlovic, Christopher Kaeufer, Birthe Gericke, Malte Feja
Summary: The development of neuroprotective therapeutics for Parkinson's disease (PD) is hindered by the lack of translation from pre-clinical to clinical trials. One strategy for improvement is to use extensively characterized animal models, such as Thy1-aSyn line 61 mice, to increase the predictive validity of pre-clinical studies. This model replicates key features of PD and has been extensively studied, leading to a better understanding of the disease and providing a platform for pre-clinical drug testing.
Article
Clinical Neurology
Alina Schidlitzki, Milos Stanojlovic, Celine Fournier, Christopher Kaeufer, Malte Feja, Birthe Gericke, Marco Garzotti, Richard W. D. Welford, Michel Alexander Steiner, Elodie Angot, Franziska Richter
Summary: This study evaluated the efficacy of Venglustat in mouse models of Parkinson's disease with alpha-synuclein overexpression. The results showed that Venglustat had differential detrimental or beneficial effects on behavior and neuropathology, possibly related to brain region-specific effects.
MOVEMENT DISORDERS
(2023)
Article
Biochemistry & Molecular Biology
Pingting Liu, Md Razaul Karim, Ana Covelo, Yuan Yue, Michael K. K. Lee, Wensheng Lin
Summary: The unfolded protein response (UPR) is a major mechanism for maintaining cellular proteostasis. It is involved in regulating neuron viability and function in neurodegenerative diseases, but its role is controversial. While evidence suggests UPR activation in neurons under normal conditions, deficiency of individual UPR branches has no major effect on brain neurons in animals. To determine the physiological role of UPR, mice with double deletion of PERK and ATF6α in neurons were generated. The results showed that UPR is required for maintaining neuronal proteostasis and the viability and function of neurons in the hippocampus of adult mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Clinical Neurology
Franziska Richter, Milos Stanojlovic, Christopher Kaeufer, Birthe Gericke, Malte Feja
Summary: The development of neuroprotective therapeutics for Parkinson's disease is hindered by the lack of translation from pre-clinical to clinical trials. Using extensively characterized animal models with validated pharmacodynamic readouts can improve the predictive validity of pre-clinical studies. The Thy1-aSyn line 61 mouse model replicates key features of sporadic Parkinson's disease and has been extensively used for pathomechanism analysis and pre-clinical drug testing, leading to more informative endpoints for trials.
Article
Medicine, Research & Experimental
Vijay K. Yadav, Julian M. Berger, Parminder Singh, Perumal Nagarajan, Gerard Karsenty
Summary: This study reveals the importance of a bone-derived embryonic hormone, osteocalcin, in regulating lifelong adrenal functions and organismal homeostasis in mice.
JOURNAL OF CLINICAL INVESTIGATION
(2022)