Article
Multidisciplinary Sciences
Kelly E. Glajch, Tim E. Moors, Yi Chen, Pascal A. Bechade, Alice Y. Nam, Molly M. Rajsombath, Thomas D. McCaffery, Ulf Dettmer, Andreas Weihofen, Warren D. Hirst, Dennis J. Selkoe, Silke Nuber
Summary: Loss-of-function mutations in GBA1 are strong genetic risk factors for Lewy body disorders, enhancing GCase activity can improve αS dyshomeostasis and reduce lipid-rich aggregates, ameliorating PD-like phenotypes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Pratibha Kumari, Dhiman Ghosh, Agathe Vanas, Yanick Fleischmann, Thomas Wiegand, Gunnar Jeschke, Roland Riek, Cedric Eichmann
Summary: This study investigated the interaction between monomeric alpha-Syn and its fibrillar form using NMR and electron paramagnetic resonance spectroscopy, revealing that intermolecular interactions reduce intramolecular contacts in monomeric alpha-Syn, leading to further unfolding of its intrinsically disordered states and critically contributing to the aggregation kinetics of alpha-Syn during secondary nucleation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Amanda Li, Cyrus Rastegar, Xiaobo Mao
Summary: Alpha-synuclein (alpha S) is a synaptic protein with extensive conformational plasticity and pathologic prion-like properties. It exists in various conformational states and can induce different pathological processes related to a class of neurodegenerative disorders called alpha-synucleinopathies. The different strains of alpha S contribute to the differential pathologies observed in patients. Understanding the conformational properties of alpha S provides insights into the overlapping yet distinct symptoms of Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies.
Editorial Material
Neurosciences
Vera I. Wiersma, Magdalini Polymenidou
Summary: The trafficking of protein aggregates through neural circuitries can lead to adverse outcomes in neurodegenerative diseases, but a beneficial aggregate-sharing strategy in microglial networks has been found to help alpha-synuclein-loaded members recover their health, as described by Scheiblich et al. in a recent issue of Cell.
Article
Medicine, Research & Experimental
Li Gao, Xinfang Xie, Pan Liu, Jing Jin
Summary: This study investigates the early assembly of transthyretin (TTR) oligomers and their interaction with tissue amyloids, leading to the formation of deposits.
Article
Chemistry, Organic
Istvan Kocsis, Elena Sanna, Christopher A. Hunter
Summary: The use of multiple dye units on the surface of vesicles significantly increases the binding affinity for α-synuclein fibrils and enhances optical response, providing a general strategy for constructing multivalent amyloid probes based on vesicles.
Review
Biochemistry & Molecular Biology
Abbie T. Rodger, Maryam A. L. Nasser, Wayne G. Carter
Summary: Currently, there are no pharmacological treatments that can completely stop or reverse the progression of Parkinson's Disease (PD). Therefore, there is a need for neuroprotective therapies. This systematic review examines the effectiveness of anti-a-synuclein (a-syn) therapies in preventing PD progression in preclinical models and human clinical trials. The review found that novel preclinical anti-a-syn therapeutics reduced a-syn aggregations and protected against dopaminergic neuronal loss. Completed clinical trials showed significant tolerability and efficacy in reducing a-syn and minimal adverse effects. Overall, this review highlights the potential of anti-a-syn therapies in both preclinical and clinical settings to reduce a-syn accumulation and potentially slow down PD progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Geriatrics & Gerontology
Silvia Paola Caminiti, Cecilia Boccalini, Nicolas Nicastro, Valentina Garibotto, Daniela Perani
Summary: We examined how sex impacts metabolic connectivity changes in probable dementia with Lewy bodies (pDLB). A total of 131 pDLB patients (58 males, 73 females) and similarly aged healthy controls (59 males, 75 females) were included in the study. Our findings showed that both male and female pDLB patients had dysfunctional hubs in specific brain regions, altered connectivity in neurotransmitter pathways, and compromised integrity of resting state networks. The study also revealed sex differences in the severity and location of connectivity alterations. These findings highlight the importance of considering sex-specific factors in understanding and managing pDLB.
NEUROBIOLOGY OF AGING
(2023)
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
Biochemistry & Molecular Biology
Jerome Lamontagne-Proulx, Katherine Coulombe, Marc Morissette, Marie Rieux, Frederic Calon, Therese Di Paolo, Denis Soulet
Summary: The mutation and overexpression of alpha-synuclein protein is associated with Parkinson's disease. The prevalence of PD is higher in men than in women, suggesting the involvement of female hormones in slowing PD progression. In mice, male individuals are more vulnerable to toxins and exhibit more severe toxicity from alpha-synuclein protein than females.
Article
Geriatrics & Gerontology
Kelly B. Menees, Rachael H. Earls, Jaegwon Chung, Janna Jernigan, Nikolay M. Filipov, Jessica M. Carpenter, Jae-Kyung Lee
Summary: This study identified gender- and age-specific alterations in splenic lymphocyte composition, circulating cytokine profiles, and NK cell phenotype and effector functions, which may help in understanding sex differences in age-related diseases, including neurodegenerative diseases like Parkinson's disease.
Article
Medicine, Research & Experimental
Emdormi Rymbai, Deepa Sugumar, Amritha Chakkittukandiyil, Ram Kothandan, Jubie Selvaraj, Divakar Selvaraj
Summary: In this study, the researchers identified cianidanol as a selective ER beta agonist and evaluated its neuroprotective effects in PD models. The results demonstrated that cianidanol showed neuroprotective effects by preventing neuronal toxicity and apoptosis, increasing the expression of key genes, and improving motor and cognitive deficits. These findings suggest that cianidanol has the potential to be a novel therapeutic agent for the treatment of PD.
Article
Biochemistry & Molecular Biology
Yasushi Imamoto, Keiichi Kojima, Ryo Maeda, Yoshinori Shichida, Toshihiko Oka
Summary: The phototransduction cascade in vertebrate rod visual cells is initiated by the photoactivation of rhodopsin and terminated by the phosphorylation of rhodopsin and binding of arrestin. This study observed the direct formation of the rhodopsin/arrestin complex using X-ray scattering. The concentration of arrestin monomer, rather than the tetramer, correlated with the rate of complex formation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Katharina Pieger, Verena Schmitt, Carina Gauer, Nadja Giessl, Iryna Prots, Beate Winner, Juergen Winkler, Johann Helmut Brandstaetter, Wei Xiang
Summary: This study identified distinct nuclear and cytosolic species of aSyn and revealed their redistribution during neuronal differentiation. Furthermore, a different distribution pattern of aSyn was observed in cells from PD patients carrying aSyn gene duplication.
Article
Multidisciplinary Sciences
B. Gegenhuber, M. Wu, R. Bronstein, J. Tollkuhn
Summary: Oestradiol establishes neural sex differences and modulates gene expression program in the mouse brain, thereby playing a role in brain development, behavior and disease.
Article
Neurosciences
Sarah E. Richards, Anna R. Moore, Alice Y. Nam, Shikhar Saxena, Suzanne Paradis, Stephen D. Van Hooser
JOURNAL OF NEUROSCIENCE
(2020)
Article
Clinical Neurology
Silke Nuber, Alice Y. Nam, Molly M. Rajsombath, Haley Cirka, Xiaoping Hronowski, Junmin Wang, Kevin Hodgetts, Liubov S. Kalinichenko, Christian P. Muller, Vera Lambrecht, Jurgen Winkler, Andreas Weihofen, Thibaut Imberdis, Ulf Dettmer, Saranna Fanning, Dennis J. Selkoe
Summary: Research shows that reducing brain SCD activity can prevent PD-like neuropathology in multiple PD models, suggesting that an orally available SCD inhibitor can effectively ameliorate PD phenotypes.
ANNALS OF NEUROLOGY
(2021)
Article
Clinical Neurology
Zhi Ruan, Dhruba Pathak, Srinidhi Venkatesan Kalavai, Asuka Yoshii-Kitahara, Satoshi Muraoka, Nemil Bhatt, Kayo Takamatsu-Yukawa, Jianqiao Hu, Yuzhi Wang, Samuel Hersh, Maria Ericsson, Santhi Gorantla, Howard E. Gendelman, Rakez Kayed, Seiko Ikezu, Jennifer Luebke, Tsuneya Ikezu
Summary: This study comprehensively characterized the physicochemical structure and pathogenic function of extracellular vesicles derived from human brains in Alzheimer's disease, prodromal Alzheimer's disease, and non-demented control cases. It was found that extracellular vesicles from Alzheimer's disease cases had higher levels of tau oligomers and exhibited more efficient propagation and misfolding of tau, suggesting a novel mechanism for tau spread in the hippocampus.
Article
Neurosciences
Maria Ericsson, Victoria von Saucken, Andrew J. Newman, Lena Doehr, Camilla Hoesch, Tae-Eun Kim, Ulf Dettmer
Summary: The study found that specific engineered missense mutations disrupt the ability of alpha-synuclein to form native multimers, leading to the accumulation of excess monomers in lipid-membrane-rich inclusions associated with neurotoxicity. These inclusions may serve as precursors to Lewy bodies, and abnormal membrane tubulation could be a relevant aspect of aberrant alpha-synuclein behavior in cells.
Correction
Neurosciences
Kevin Clayton, Jean Christophe Delpech, Shawn Herron, Naotoshi Iwahara, Maria Ericsson, Takashi Saito, Takaomi C. Saido, Seiko Ikezu, Tsuneya Ikezu
Summary: The paper has been revised and the revised version can be accessed through the original article.
MOLECULAR NEURODEGENERATION
(2021)
Article
Neurosciences
Kevin Clayton, Jean Christophe Delpech, Shawn Herron, Naotoshi Iwahara, Maria Ericsson, Takashi Saito, Takaomi C. Saido, Seiko Ikezu, Tsuneya Ikezu
Summary: Our findings suggest that MGnD microglia hyper-secrete p-tau(+) EVs while compacting A beta plaques and clearing NP tau, which we propose as a novel mechanistic link between amyloid plaque deposition and exacerbation of tau propagation in App(NL-G-F) mice.
MOLECULAR NEURODEGENERATION
(2021)
Article
Multidisciplinary Sciences
Kelly E. Glajch, Tim E. Moors, Yi Chen, Pascal A. Bechade, Alice Y. Nam, Molly M. Rajsombath, Thomas D. McCaffery, Ulf Dettmer, Andreas Weihofen, Warren D. Hirst, Dennis J. Selkoe, Silke Nuber
Summary: Loss-of-function mutations in GBA1 are strong genetic risk factors for Lewy body disorders, enhancing GCase activity can improve αS dyshomeostasis and reduce lipid-rich aggregates, ameliorating PD-like phenotypes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Luis Fonseca-Ornelas, Thibault Viennet, Matteo Rovere, Haiyang Jiang, Lei Liu, Silke Nuber, Maria Ericsson, Haribabu Arthanari, Dennis J. Selkoe
Summary: The study shows that the misfolding of alpha-synuclein is linked to the pathogenesis of Parkinson's disease, leading to abnormalities in Ca2+-dependent vesicle exocytosis and synaptic vesicle ultrastructure. The altered conformation of alpha-synuclein may be an early cause of synaptotoxicity in synucleinopathies.
Article
Critical Care Medicine
Gareth R. Willis, Monica Reis, Ali Hashemi Gheinani, Angeles Fernandez-Gonzalez, Elizabeth S. Taglauer, Vincent Yeung, Xianlan Liu, Maria Ericsson, Eric Haas, S. Alex Mitsialis, Stella Kourembanas
Summary: MEx therapy can ameliorate hyperoxia-induced neonatal lung injury by improving core histological features, localizing in the lung and interacting with myeloid cells, restoring the proportion of alveolar macrophages and suppressing inflammatory cytokine production, promoting an immunosuppressive BMDMy phenotype through phenotypic and epigenetic reprogramming, and driving the immunosuppressive actions of BMDMy to restore lung structure, attenuate fibrosis and pulmonary vascular remodeling, and enhance exercise capacity.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2021)
Article
Biology
Alice Nam, Selorm Quarshie, Matthew Kimble, David A. Hessinger
Summary: Cnidarians rely on mechanical stimuli to trigger nematocyst discharge and feeding behaviors. This study investigated the involvement of transient receptor potential (TRP) channels in nematocyst discharge. The results suggest that a TRPV-like homolog plays an essential role in nematocyst-mediated prey killing from one type of cnidocytes, while other TRP channels are likely involved in discharge from different types of cnidocytes.
BIOLOGICAL BULLETIN
(2022)
Article
Clinical Neurology
Andrew M. Stern, Lei Liu, Shanxue Jin, Wen Liu, Angela L. Meunier, Maria Ericsson, Michael B. Miller, Megan Batson, Tingwan Sun, Sagar Kathuria, David Reczek, Laurent Pradier, Dennis J. Selkoe
Summary: Researchers have developed a new monoclonal antibody that specifically targets neurotoxic oligomers of amyloid-beta peptide. This antibody has a unique property that allows it to isolate soluble amyloid-beta aggregates from Alzheimer's disease brain without denaturation. These aggregates may be the principal neurotoxic forms of amyloid-beta in Alzheimer's disease, and they can lead to various pathological events.
Article
Microbiology
Adam J. Hume, Baylee Heiden, Judith Olejnik, Ellen L. Suder, Stephen Ross, Whitney A. Scoon, Esther Bullitt, Maria Ericsson, Mitchell R. White, Jacquelyn Turcinovic, Tran T. N. Thao, Ryan M. Hekman, Joseph E. Kaserman, Jessie Huang, Konstantinos-Dionysios Alysandratos, Gabor E. Toth, Ferenc Jakab, Darrell N. Kotton, Andrew A. Wilson, Andrew Emili, Volker Thiel, John H. Connor, Gabor Kemenesi, Daniel Cifuentes, Elke Muhlberger
Summary: Next generation sequencing has helped identify and study RNA viruses in animal hosts that have the potential to infect humans. In this study, researchers successfully used a minigenome system to rescue and study an uncultured filovirus called Lloviu virus (LLOV), which is closely related to Ebola virus. They were able to generate recombinant LLOV and study its replication, infection, and response to antiviral drugs. This research provides valuable insights into the pathogenic potential of LLOV and could aid in pandemic preparedness.
Article
Virology
Mariano Carossino, Devin Kenney, Aoife K. O'Connell, Paige Montanaro, Anna E. Tseng, Hans P. Gertje, Kyle A. Grosz, Maria Ericsson, Bertrand R. Huber, Susanna A. Kurnick, Saravanan Subramaniam, Thomas A. Kirkland, Joel R. Walker, Kevin P. Francis, Alexander D. Klose, Neal Paragas, Markus Bosmann, Mohsan Saeed, Udeni B. R. Balasuriya, Florian Douam, Nicholas A. Crossland
Summary: This study evaluated the pathogenesis and clinical dynamics of SARS-CoV-2 infection in a transgenic mouse model. The results suggest that the model has limitations in replicating the pathological processes, neuroinvasion, and neurodissemination observed in humans.
Article
Virology
Adrian R. Wilkie, Mayuri Sharma, Margaret Coughlin, Jean M. Pesola, Maria Ericsson, Jessica L. Lawler, Rosio Fernandez, Donald M. Coen
Summary: The study found that the nucleoplasmic subunit UL53 of the HCMV NEC has some associations with myosin Va and capsids, but contrary to other herpesviruses, UL53 is not important for the migration of capsids towards the inner nuclear membrane.
Article
Multidisciplinary Sciences
Yang You, Zhengrong Zhang, Nadia Sultana, Maria Ericsson, Yuka A. Martens, Min Sun, Takahisa Kanekiyo, Seiko Ikezu, Scott A. Shaffer, Tsuneya Ikezu
Summary: This study demonstrates that ATP1A3 is a reliable biomarker for neuron-derived extracellular vesicles (NDEVs) and shows higher enrichment of cargo proteins relevant to Alzheimer's disease. It suggests that ATP1A3 can be used as a diagnostic target for neurological diseases.