Article
Engineering, Biomedical
Loredana Leggio, Francesca L'Episcopo, Andrea Magri, Maria Jose Ulloa-Navas, Greta Paterno, Silvia Vivarelli, Carlos A. P. Bastos, Cataldo Tirolo, Nunzio Testa, Salvatore Caniglia, Pierpaolo Risiglione, Fabrizio Pappalardo, Alessandro Serra, Patricia Garcia-Tarraga, Nuno Faria, Jonathan J. Powell, Luca Peruzzotti-Jametti, Stefano Pluchino, Jose Manuel Garcia-Verdugo, Angela Messina, Bianca Marchetti, Nunzio Iraci
Summary: Extracellular vesicles released by astrocytes in the brain of Parkinson's disease patients play a significant role in cell-to-cell communication and have neuroprotective effects on dopaminergic neurons. Nigrostriatal astrocytes release the highest number of EVs, especially in response to CCL3, which promotes dopaminergic neuroprotection. These EVs specifically protect differentiated cells from oxidative stress-induced caspase-3 activation and restore impaired mitochondrial function caused by the neurotoxin MPP+. EVs from VMB-astrocytes fully restore ATP production in differentiated SH-SY5Y cells.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Erica Staurenghi, Valentina Cerrato, Paola Gamba, Gabriella Testa, Serena Giannelli, Valerio Leoni, Claudio Caccia, Annalisa Buffo, Wendy Noble, Beatriz Gomez Perez-Nievas, Gabriella Leonarduzzi
Summary: Among the brain hallmarks of Alzheimer's disease, reactive astrocytes are correlated with neuronal loss and cognitive deficits, while alterations in brain cholesterol metabolism contribute to AD pathogenesis. Oxysterols in AD brains induce astrocyte reactivity and the release of mediators that impact neuronal health and synapses, with lipocalin-2 playing a key role in mediating the synaptotoxic effect of oxysterol-treated astrocytes.
Article
Biochemistry & Molecular Biology
Katie Peppercorn, Torsten Kleffmann, Stephanie M. Hughes, Warren P. Tate
Summary: sAPPa modulates the proteome and secretome of astrocytes, which are involved in neurogenesis, synaptogenesis, synaptic plasticity, and have implications in Alzheimer's disease and normal brain physiology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Weizong Wang, Yixin Zhao, Huilin Li, Yujiao Zhang, Xiaomeng Jia, Cong Wang, Pengju Zhu, Jiangrong Wang, Yinglong Hou
Summary: This study demonstrates that MSC-derived exosomes can enhance the proliferation, migration, and tube formation ability of umbilical vein endothelial cells (HUVECs) in vitro, as well as inhibit apoptosis induced by rapamycin. Furthermore, a distinct class of exosomal miRNAs, including six miRNAs closely related to neovasculogenesis, was identified.
EXPERIMENTAL CELL RESEARCH
(2021)
Article
Neurosciences
Yongang Li, Jiachen Gu, Youbing Mao, Xijia Wang, Zongshan Li, Xiaomin Xu, Huimin Chen, Yaxing Gui
Summary: This study examined the role of cerebrospinal fluid (CSF) exosomes from patients with autoimmune encephalitis (AE) and herpes simplex encephalitis (HSE). The study found specific miRNAs highly expressed in AE patients and higher exosome concentration in CSF of HSE patients. Furthermore, the research suggests that HSV may trigger brain autoimmunity in HSE through the presentation of surface autoantigens via exosomes.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Roberto Stella, Raphael Severino Bonadio, Stefano Cagnin, Maria Lina Massimino, Alessandro Bertoli, Caterina Peggion
Summary: This study investigated the proteomic profile and secreted metabolome of ALS astrocytes derived from transgenic mouse models, revealing depleted proteins and secreted metabolites involved in glutathione metabolism and signaling, as well as altered transcription factor activation and lipid metabolism in ALS astrocytes expressing mutated hSOD1. These findings provide insights into potential therapeutic targets to address astrocyte dysfunctionalities and altered astrocyte-MN crosstalk in ALS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Byung Geun Ha, Jung-Yoon Heo, Yu-Jin Jang, Tae-Shin Park, Ju-Yeon Choi, Woo Young Jang, Sung-Jin Jeong
Summary: The study revealed that mitochondrial dysfunction in astrocytes of FXS model mice is associated with the pathogenesis of the disease, and can be monitored by depletion of mitochondrial components in EVs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Michail Spiliopoulos, Andrew Haddad, Huda B. Al-Kouatly, Saeed Haleema, Michael J. Paidas, Sara N. Iqbal, Robert Glazer
Summary: The study aims to compare the expression profile of microRNAs in the peripheral blood of pregnant women with preterm premature rupture of membranes (PPROM) and healthy pregnant women. The results show that there are significant differences in microRNA expression between PPROM patients and healthy pregnancies, which are associated with altered collagen and matrix metalloprotease expression in the extracellular matrix.
Article
Cell Biology
Xiaoqiang Wu, Zhiwei Wang, Junpeng Wang, Xiangyong Tian, Guanghui Cao, Yue Gu, Fengmin Shao, Tianzhong Yan
Summary: The study revealed that DANCR in BM MSC-Ex promotes Treg cell differentiation and induces immune tolerance of kidney transplantation by down-regulating SIRT1 expression in CD4(+) T cells.
Article
Geriatrics & Gerontology
Jana Tureckova, Monika Kamenicka, Denisa Kolenicova, Tereza Filipi, Zuzana Hermanova, Jan Kriska, Lenka Meszarosova, Barbora Pukajova, Lukas Valihrach, Peter Androvic, Daniel Zucha, Martina Chmelova, Lydia Vargova, Miroslava Anderova
Summary: This study reveals the impact of amyloid-beta toxicity and tau pathology on astrocyte swelling, volume recovery, and extracellular space diffusion in a mouse model of Alzheimer's disease. AD progression affects astrocyte ionic/neurotransmitter uptake, leading to enlarged extracellular space and increased obstacles. These changes may disrupt intercellular communication and contribute to cytotoxicity.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Cell Biology
Song Li, Tatjana C. Jakobs
Summary: Aging leads to decline in neuronal function, but protecting astrocytes can slow down this decline and protect visual function.
Article
Neurosciences
Cory R. Reiter, Rima Rebiai, Angelika Kwak, Jeff Marshall, Dylan Wozniak, Giusepe Scesa, Duc Nguyen, Emily Rue, Chandimal Pathmasiri, Robert Pijewski, Richard van Breemen, Stephanie Cologna, Stephen J. Crocker, M. Irene Givogri, Ernesto R. Bongarzone
Summary: This study found that Psychosine is associated with secreted extracellular vesicles (EVs) and reducing EV secretion in the brain of Twitcher mice led to increased disease severity. The results suggest the secretion of pathogenic lipids via EV pathways and highlight the relevance of this mechanism in spreading pathogenic lipids in neurological lipidoses.
Review
Cell & Tissue Engineering
Catherine Hering, Ashok K. Shetty
Summary: This review discusses the therapeutic efficacy of extracellular vesicles (EVs) derived from neural stem cells (NSC-EVs), astrocytes (ADEVs), and microglia (MDEVs) in traumatic brain injury (TBI) models. NSC-EV or ADEV therapy has been shown to mediate neuroprotective effects and improve motor and cognitive function after TBI. However, the therapeutic effects of naive MDEVs are yet to be tested rigorously in TBI models.
STEM CELLS TRANSLATIONAL MEDICINE
(2023)
Review
Medicine, Research & Experimental
Feng Lin, Suihao Zhang, Xia Liu, Meishan Wu
Summary: Exosomal miR-125b-5p from BMSCs inhibits atherosclerotic plaque formation by targeting Map4k4 expression, leading to reduced inflammation, decreased blood lipid levels, smaller plaque areas, increased expression of smooth muscle cell marker α-SMA, as well as inhibition of apoptosis in AS mice.
Article
Biochemistry & Molecular Biology
Maya Maor-Nof, Zohar Shipony, Rodrigo Lopez-Gonzalez, Lisa Nakayama, Yong-Jie Zhang, Julien Couthouis, Jacob A. Blum, Patricia A. Castruita, Gabriel R. Linares, Kai Ruan, Gokul Ramaswami, David J. Simon, Aviv Nof, Manuel Santana, Kyuho Han, Nasa Sinnott-Armstrong, Michael C. Bassik, Daniel H. Geschwind, Marc Tessier-Lavigne, Laura D. Attardi, Thomas E. Lloyd, Justin K. Ichida, Fen-Biao Gao, William J. Greenleaf, Jennifer S. Yokoyama, Leonard Petrucelli, Aaron D. Gitler
Summary: The repeat expansion in the C9orf72 gene leads to activation of a specific transcriptional program, causing neurodegeneration. Removing p53 in experiments successfully rescued neuronal degeneration and extended survival.
Article
Neurosciences
Jacob A. Blum, Sandy Klemm, Jennifer L. Shadrach, Kevin A. Guttenplan, Lisa Nakayama, Arwa Kathiria, Phuong T. Hoang, Olivia Gautier, Julia A. Kaltschmidt, William J. Greenleaf, Aaron D. Gitler
Summary: This study analyzed single-nucleus transcriptomes from the adult mouse spinal cord, revealing heterogeneity in skeletal motor neurons and identifying a novel transcriptional subpopulation. The data provide important insights into investigating the molecular logic of adult motor neuron diversity and the cellular and molecular basis of motor neuron function in health and disease.
NATURE NEUROSCIENCE
(2021)
Editorial Material
Biochemistry & Molecular Biology
Steven Boeynaems, Aaron D. Gitler
TRENDS IN BIOCHEMICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Valerio Napolioni, Carolyn A. Fredericks, Yongha Kim, Divya Channappa, Raiyan R. Khan, Lily H. Kim, Faria Zafar, Julien Couthouis, Guido A. Davidzon, Elizabeth C. Mormino, Aaron D. Gitler, Thomas J. Montine, Birgitt Schule, Michael D. Greicius
Summary: This study investigates the clinical and neuropathologic features of patients with Lewy body spectrum disorder (LBSD) carrying a nonsense variant in the GBA gene. Through literature review and case analysis, it suggests a potential pathogenic role of the GBA p.R202X mutation in LBSD, demonstrating clinical and pathological heterogeneity.
Article
Genetics & Heredity
Sarah J. Eger, Yann Le Guen, Raiyan R. Khan, Jacob N. Hall, Gabriel Kennedy, Greg Zaharchuk, Julien Couthouis, William S. Brooks, Dennis Velakoulis, Valerio Napolioni, Michael E. Belloy, Clifton L. Dalgard, Elizabeth C. Mormino, Aaron D. Gitler, Michael D. Greicius
Summary: This study confirms the pathogenicity of the F386L PSEN1 variant and highlights the importance of studying families from underrepresented populations.
NEUROLOGY-GENETICS
(2022)
Article
Multidisciplinary Sciences
X. Rosa Ma, Mercedes Prudencio, Yuka Koike, Sarat C. Vatsavayai, Garam Kim, Fred Harbinski, Adam Briner, Caitlin M. Rodriguez, Caiwei Guo, Tetsuya Akiyama, H. Broder Schmidt, Beryl B. Cummings, David W. Wyatt, Katherine Kurylo, Georgiana Miller, Shila Mekhoubad, Nathan Sallee, Gemechu Mekonnen, Laura Ganser, Jack D. Rubien, Karen Jansen-West, Casey N. Cook, Sarah Pickles, Bjorn Oskarsson, Neill R. Graff-Radford, Bradley F. Boeve, David S. Knopman, Ronald C. Petersen, Dennis W. Dickson, James Shorter, Sua Myong, Eric M. Green, William W. Seeley, Leonard Petrucelli, Aaron D. Gitler
Summary: A hallmark feature of ALS and FTD is the depletion of RNA-binding protein TDP-43 from neurons, and a major function of TDP-43 is to repress cryptic exon inclusion. UNC13A gene polymorphisms are strongly associated with FTD and ALS, and this study shows that loss of TDP-43 leads to cryptic exon splicing in UNC13A. The top genetic risk factors for FTD and ALS (UNC13A genetic variants) are shown to be functionally linked to TDP-43 dysfunction.
Editorial Material
Neurosciences
Kevin A. Guttenplan, Aaron D. Gitler
Summary: This study reveals polyphosphate (polyP) as an unexpected factor that may drive neurodegeneration by causing neuronal death in amyotrophic lateral sclerosis.
Review
Genetics & Heredity
Jacob A. Blum, Aaron D. Gitler
Summary: Motor neurons are a powerful cell type in the central nervous system, controlling muscle contraction throughout the body. Understanding the heterogeneity of motor neurons in adult organisms is crucial for understanding diseases and spinal cord injuries. The development of high-throughput single-cell transcriptomics has revealed remarkable transcriptional diversity within the skeletal and autonomic nervous systems.
TRENDS IN GENETICS
(2022)
Editorial Material
Oncology
Tetsuya Akiyama, Yuka Koike, Leonard Petrucelli, Aaron D. Gitler
Summary: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurodegenerative diseases characterized by depletion of the RNA-binding protein TDP-43. TDP-43 plays a vital role in repressing the inclusion of cryptic exons during RNA splicing. Understanding and targeting these cryptic splicing events may have significant implications for the diagnosis and treatment of ALS and FTD.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Editorial Material
Biochemistry & Molecular Biology
Garam Kim, Aaron D. Gitler
Summary: In this study, the researchers demonstrate APOE-driven cell-type-specific changes that may contribute to the increased risk of Alzheimer's disease.
Article
Multidisciplinary Sciences
Keren Lasker, Steven Boeynaems, Vinson Lam, Daniel Scholl, Emma Stainton, Adam Briner, Maarten Jacquemyn, Dirk Daelemans, Ashok Deniz, Elizabeth Villa, Alex S. Holehouse, Aaron D. Gitler, Lucy Shapiro
Summary: Intracellular phase separation is a universal principle for organizing biochemical reactions. The material properties of condensates formed by the protein PopZ in Caulobacter crescentus are determined by a balance between attractive and repulsive forces. Disrupting this balance results in condensates with different material properties. Condensates with specific material properties are important for proper cell division and organismal fitness.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Caitlin M. Rodriguez, Sophia C. Bechek, Graham L. Jones, Lisa Nakayama, Tetsuya Akiyama, Garam Kim, David E. Solow-Cordero, Stephen M. Strittmatter, Aaron D. Gitler
Summary: Gene-based therapeutic strategies to lower ataxin-2 levels are emerging for ALS and SCA2. This study identifies RTN4R as a potent modifier of ataxin-2 levels, and demonstrates that reducing RTN4R expression or using a peptide inhibitor can lower ataxin-2 protein levels. Additionally, it is found that both ataxin-2 and RTN4/NoGo-Receptor play a role in limiting axonal regeneration.
Article
Cell Biology
Garam Kim, Lisa Nakayama, Jacob A. Blum, Tetsuya Akiyama, Steven Boeynaems, Meenakshi Chakraborty, Julien Couthouis, Eduardo Tassoni-Tsuchida, Caitlin M. Rodriguez, Michael C. Bassik, Aaron D. Gitler
Summary: A study has found that genes encoding components of the lysosomal vacuolar ATPase (v-ATPase) can modify levels of ataxin-2 protein, and small molecule v-ATPase inhibitors approved by the FDA can lower ataxin-2 protein levels. This discovery suggests v-ATPase as a potential drug target for ALS and SCA2.
Editorial Material
Biochemistry & Molecular Biology
Caiwei Guo, Aaron D. Gitler
Summary: This study reveals how the cellular background influences the formation of toxic aggregates of the Huntington's disease protein, providing new insights into selective neuronal vulnerability in neurodegenerative diseases.
Article
Cell Biology
Ehsan Dadgar-Kiani, Gregor Bieri, Ronald Melki, Aaron D. Gitter, Jin Hyung Lee
Summary: This study used whole-brain tissue clearing and high-resolution imaging to map the spreading of α-synuclein pathology in a Parkinson's disease model. A computational model was developed to accurately predict the spreading patterns, providing insights into disease progression and potential therapeutic interventions.