Article
Biochemistry & Molecular Biology
Nicholas Brookhouser, Sreedevi Raman, Carlye Frisch, Gayathri Srinivasan, David A. Brafman
Summary: The study revealed that the APOE2 variant reduces the risk of developing Alzheimer's disease and showed that converting APOE3 to APOE2 significantly decreased the production of amyloid-beta peptides. Furthermore, it was demonstrated that the protective effects of APOE2 may be related to a mechanism involving non-amyloidogenic processing.
MOLECULAR PSYCHIATRY
(2021)
Article
Environmental Sciences
Yan Huang, Lulu Guo, Chulin Cao, Rui Ma, Yuting Huang, Kai Zhong, Hong Gao, Yina Huang, Qian Bu
Summary: This study investigated the neurotoxic effects of silver nanoparticles (AgNPs) on cerebral organoids derived from induced pluripotent stem cells. The results showed that at low concentrations, AgNPs increased cell proliferation and inhibited neural apoptosis, but impaired cilium assembly and elongation, leading to abnormal organoid growth. At high concentrations, AgNPs significantly inhibited cell proliferation and induced apoptosis, disrupting the expression and co-localization of cytoskeleton proteins and perturbing neurite growth. Overall, AgNPs exposure can induce developmental neurotoxic effects in cerebral organoids and may be a potential congenital risk factor.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
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)
Review
Biochemistry & Molecular Biology
Miren Altuna, Gonzalo Olmedo-Saura, Maria Carmona-Iragui, Juan Fortea
Summary: There is a close relationship between epilepsy and Alzheimer's disease, with shared pathophysiological processes and potential biomarker effects. The presence of epilepsy in Alzheimer's disease may accelerate cognitive decline, and the diagnosis of clinical seizures in Alzheimer's disease is challenging.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Hsiao-Lung An, Hung-Chih Kuo, Tang K. Tang
Summary: Researchers generated human induced pluripotent stem cells (hiPSCs) carrying a mutant centrosomal protein using CRISPR/Cas9 gene editing technology. The mutant protein disrupted the recruitment of centriolar proteins involved in centriole elongation and resulted in the production of short centrioles and long cilia. Additionally, the mutant protein induced neuronal cell death and premature neuronal differentiation, leading to smaller brain organoids resembling the phenotype of microcephaly. These findings provide insights into the pathogenic mechanisms of MCPH.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Sai Sreenivasamurthy, Mahek Laul, Nan Zhao, Tiffany Kim, Donghui Zhu
Summary: Alzheimer's disease is a progressive neurodegenerative disease associated with aging. Two-dimensional cell culture and animal models have contributed to our understanding of the disease mechanism, but they cannot fully capture the complexity of human brain tissue. The emergence of three-dimensional cerebral organoid models offers a more accurate representation of human brain tissue.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Review
Neurosciences
Feng-Chen Bi, Xin-He Yang, Xiao-Yu Cheng, Wen-Bin Deng, Xiao-Li Guo, Hui Yang, Yin Wang, Juan Li, Yao Yao
Summary: This review discusses the advantages, limitations, and possible solutions of Alzheimer's disease cerebral organoid system in comparison to commonly used models, aiming to improve their application in research. Ethical concerns associated with human cerebral organoids are also addressed, along with summarizing future directions for studies to enhance the system in modeling pathological events observed in Alzheimer's disease brains.
TRANSLATIONAL NEURODEGENERATION
(2021)
Article
Chemistry, Multidisciplinary
Jibo Wang, Haowen Qiao, Zhenyan Wang, Wen Zhao, Tao Chen, Bin Li, Lili Zhu, Sihan Chen, Longjun Gu, Ying Wu, Zhentao Zhang, Linlin Bi, Pu Chen
Summary: This article demonstrates a rational design of human-sourced brain-like cortical tissue models through reverse engineering and bionic design. The acoustic assembly technique is employed to assemble hiPSC-derived neural progenitors and neurons separately in a label-free and contact-free manner, followed by subsequent neural differentiation and culture. The generated microtissues encapsulate the neuronal microanatomy of human cerebral-cortex tissue, including six-layered neuronal architecture, synaptic connections between interlayers, and neuroelectrophysiological transmission. Furthermore, these microtissues are infected with herpes simplex virus type I (HSV-1) virus, and the HSV-induced pathogenesis associated with Alzheimer's disease is determined. A high-fidelity human-relevant in vitro histotypic model is provided for the cerebral cortex, which will facilitate wide applications in probing the mechanisms of neurodegenerative diseases and screening the candidates for neuroprotective agents.
ADVANCED MATERIALS
(2023)
Article
Cell Biology
Fabia Febbraro, Helena Hordum Breum Andersen, Meagan M. Kitt, Thomas E. Willnow
Summary: VPS10P domain receptors play a crucial role in psychiatric and neurodegenerative diseases. The study revealed distinct temporal, spatial, and subcellular expression patterns of different receptor species in the human brain. This provides valuable insights into the impact of receptor function on behavioral and cognitive defects in the human brain.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Santiago Ramirez, Abhisek Mukherjee, Sofia Sepulveda, Andrea Becerra-Calixto, Nicolas Bravo-Vasquez, Camila Gherardelli, Melissa Chavez, Claudio Soto
Summary: The study successfully adapted the controlled cortical impact (CCI) model for inducing traumatic brain injury (TBI) in human cerebral organoids (COs) derived from induced pluripotent stem cells (iPSCs), showing that COs recapitulate primary pathological changes of TBI. This novel approach using human COs in vitro holds great potential for understanding and treating TBI.
Article
Cell Biology
Ram Sagar, Ioannis Azoidis, Cristina Zivko, Ariadni Xydia, Esther S. Oh, Paul B. Rosenberg, Constantine G. Lyketsos, Vasiliki Mahairaki, Dimitrios Avramopoulos
Summary: Recent advances in generating pluripotent stem cells from somatic cells and differentiating them into various cell types have allowed us to study these cells without the limitations of disease-related changes. By creating induced pluripotent stem cells (iPSCs) from Alzheimer's disease (AD) patients and controls, and differentiating them into glutamatergic neurons, our RNA sequencing analysis identified 621 differentially expressed genes between AD and control neurons. These genes have significant overlap with those reported in a single-cell transcriptome study of AD patients, including five genes associated with AD from genome-wide association studies, suggesting their involvement in a larger functional network.
Article
Neurosciences
Ranmal A. Samarasinghe, Osvaldo A. Miranda, Jessie E. Buth, Simon Mitchell, Isabella Ferando, Momoko Watanabe, Thomas F. Allison, Arinnae Kurdian, Namie N. Fotion, Michael J. Gandal, Peyman Golshani, Kathrin Plath, William E. Lowry, Jack M. Parent, Istvan Mody, Bennett G. Novitch
Summary: This paper explores neural network and cellular complexity within human cortical and subcortical fusion organoids, revealing network dysfunction associated with Rett syndrome. The findings demonstrate the potential of brain organoids in modeling human neurological diseases and the utility in therapeutic discovery.
NATURE NEUROSCIENCE
(2021)
Review
Cell Biology
Olivia Krefft, Philipp Koch, Julia Ladewig
Summary: Genetic studies have identified mutations associated with malformations of cortical development in humans, and human brain organoids derived from pluripotent stem cells are used as a model to investigate these mechanisms. This model provides insights into the underlying pathomechanisms of MCD, reflecting the phenotypic features of these diseases.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2021)
Article
Neurosciences
Jan T. Czerminski, Oliver D. King, Jeanne B. Lawrence
Summary: This study uses cortical organoids as a model to explore the early fetal brain development in Down syndrome. The results indicate that even with better control of organoid and batch variability, variation between isogenic cell lines may obscure or be conflated with subtle neurodevelopmental phenotypes that may present in the second/third trimester of DS brain development.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Yueqi Wang, Simone Chiola, Guang Yang, Chad Russell, Celeste J. Armstrong, Yuanyuan Wu, Jay Spampanato, Paisley Tarboton, H. M. Arif Ullah, Nicolas U. Edgar, Amelia N. Chang, David A. Harmin, Vittoria Dickinson Bocchi, Elena Vezzoli, Dario Besusso, Jun Cui, Elena Cattaneo, Jan Kubanek, Aleksandr Shcheglovitov
Summary: The study generated human brain organoids from stem cell-derived isolated single neural rosettes to investigate human cortico-striatal development and deficits caused by abnormalities in the SHANK3 gene.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Swagata Ghatak, Nima Dolatabadi, Richard Gao, Yin Wu, Henry Scott, Dorit Trudler, Abdullah Sultan, Rajesh Ambasudhan, Tomohiro Nakamura, Eliezer Masliah, Maria Talantova, Bradley Voytek, Stuart A. Lipton
Summary: Early stages of human Alzheimer's disease (AD) show hyperexcitability in the brain, leading to extensive synapse loss and cognitive dysfunction, with no current disease-modifying therapy available. Utilizing human iPSC models may be a valuable tool for screening drugs to treat hyperexcitability and synaptic damage in AD, potentially increasing the chances of success in treatment.
MOLECULAR PSYCHIATRY
(2021)
Review
Pharmacology & Pharmacy
Swagata Ghatak, Maria Talantova, Scott R. McKercher, Stuart A. Lipton
Summary: The balance between excitation and inhibition in a neuronal network, known as excitatory/inhibitory (E/I) balance, is crucial for normal brain function. In pathological conditions, this balance can be disrupted, leading to E/I imbalance and network dysfunction. Developing therapies to rebalance neural networks is important for improving neurological function in diseases associated with E/I imbalance.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 61, 2021
(2021)
Article
Neurosciences
Dorit Trudler, Sara Sanz-Blasco, Yvonne S. Eisele, Swagata Ghatak, Karthik Bodhinathan, Mohd Waseem Akhtar, William P. Lynch, Juan C. Pina-Crespo, Maria Talantova, Jeffery W. Kelly, Stuart A. Lipton
Summary: In Parkinson's disease, synaptic and neuronal loss are prominent features. The study reveals that alpha Syn oligomers induce excessive glutamate release from astrocytes, activating NMDARs on neurons and leading to synaptic damage. However, the drug NitroSynapsin shows promise in protecting synapses from alpha Syn-induced damage.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Stuart A. Lipton, Paschalis-Thomas Doulias, Tomohiro Nakamura, Henry Scott, Abdullah Sultan, Scott R. McKercher, Amanda Deal, Matthew Albertolle, Harry Ischiropoulos
Summary: Both HIV-1 and methamphetamine use lead to increased oxidative and nitrosative stress in the brain, potentially contributing to cognitive impairment and worsening effects of drug abuse. Enhanced S-nitrosylation of proteins derived from nitric oxide may disrupt protein activity, particularly impacting TCA enzymes and leading to energy collapse observed in HAND and methamphetamine use.
JOURNAL OF NEUROVIROLOGY
(2021)
Article
Multidisciplinary Sciences
Dorit Trudler, Kristopher L. Nazor, Yvonne S. Eisele, Titas Grabauskas, Nima Dolatabadi, James Parker, Abdullah Sultan, Zhenyu Zhong, Marshall S. Goodwin, Yona Levites, Todd E. Golde, Jeffery W. Kelly, Michael R. Sierks, Nicholas J. Schork, Michael Karin, Rajesh Ambasudhan, Stuart A. Lipton
Summary: Parkinson's disease is associated with the accumulation of alpha-synuclein and activation of microglia, potentially leading to neuronal death. This study shows that alpha-synuclein can activate NLRP3 inflammasome in human microglia and that alpha-synuclein-antibody complexes can exacerbate inflammation in a human context.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Tomohiro Nakamura, Chang-ki Oh, Xu Zhang, Stuart A. Lipton
Summary: Neurodegenerative disorders such as Alzheimer's and Parkinson's diseases are characterized by progressive degeneration of synapses and neurons, often attributed to accumulated misfolded/aggregated proteins. Excessive reactive oxygen and nitrogen species in the brain may contribute to protein misfolding, potentially exacerbated by genetic mutations and environmental factors. Understanding the role of reactive nitrogen species in post-translational modifications of proteins could lead to therapeutic interventions for neurodegenerative diseases.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Immunology
Hongxu Xian, Yuan Liu, Alexandra Rundberg Nilsson, Raphaella Gatchalian, Timothy R. Crother, Warren G. Tourtellotte, Yi Zhang, German R. Aleman-Muench, Gavin Lewis, Weixuan Chen, Sarah Kang, Melissa Luevanos, Dorit Trudler, Stuart A. Lipton, Pejman Soroosh, John Teijaro, Juan Carlos de la Torre, Moshe Arditi, Michael Karin, Elsa Sanchez-Lopez
Summary: The study found that metformin can attenuate COVID-19-induced ARDS by inhibiting NLRP3 inflammasome activation, IL-1 beta and IL-6 secretion, and by blocking ATP and mtDNA synthesis.
Review
Biochemistry & Molecular Biology
Dorit Trudler, Swagata Ghatak, Stuart A. Lipton
Summary: Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, represent a significant social and economic burden due to increasing prevalence and lack of effective therapies. Lack of reliable models has hindered the development of treatments, but human-induced pluripotent stem cell technology offers a promising alternative to complement animal models for disease modeling and drug discovery.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Chang-Ki Oh, Nima Dolatabadi, Piotr Cieplak, Maria T. Diaz-Meco, Jorge Moscat, John P. Nolan, Tomohiro Nakamura, Stuart A. Lipton
Summary: This article investigates the mechanism by which dysregulation of autophagic pathways leads to the accumulation of abnormal proteins and damaged organdies in neurodegenerative disorders. The authors found that pathologic protein S-nitrosylation of p62 is a critical factor for autophagic inhibition and cell-to-cell spread.
JOURNAL OF NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Takumi Satoh, Dorit Trudler, Chang-Ki Oh, Stuart A. Lipton
Summary: This article reviews the potential applications of carnosic acid (CA) and carnosol (CS) in rosemary for conditions such as Alzheimer's disease, Parkinson's disease, and COVID-19. It highlights the antioxidant, anti-inflammatory, and neuroprotective effects of CA, as well as its potential to inhibit the NLRP3 inflammasome. The article suggests that CA-related compounds could serve as therapeutics for acute and chronic neurological effects caused by SARS-CoV-2 infection and other neurodegenerative diseases.
Article
Biochemistry & Molecular Biology
Ki-Ryeong Kim, Eun-Jung Cho, Jae-Won Eom, Sang-Seok Oh, Tomohiro Nakamura, Chang-ki Oh, Stuart A. Lipton, Yang-Hee Kim
Summary: This study reveals that S-nitrosylation of lysosomal protease cathepsin B (CTSB) inhibits its activity, blocks autophagic flux, and contributes to the pathogenesis of Alzheimer's disease (AD).
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Medicine, General & Internal
Ritin Mohindra, Mohata Madhav, Vikas Suri, Krishna Divyashree
Summary: Rabies is a fatal disease causing motor and autonomic dysfunction. Involvement of the limbic system is rare, and limited data exists on its prevalence. This case highlights the importance of considering rabies encephalitis in patients with limbic system symptoms, as early diagnosis can lead to appropriate public health measures and reduced risk of infection.
