Review
Multidisciplinary Sciences
Baljit S. Khakh, Steven A. Goldman
Summary: Huntington's disease (HD) is a fatal neurodegenerative disease caused by a mutation in the huntingtin gene. Astrocytes in the striatum, a brain region affected in HD, play a role in the pathology of the disease. Dysfunctions in astrocytes contribute to cellular and metabolic abnormalities in HD, suggesting the potential for therapeutic targeting of these cells to restore normal function.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Article
Cell Biology
Abdalla M. Albeely, Olivia O. F. Williams, Melissa L. Perreault
Summary: The study suggests that increased activity of GSK-3 beta (S9A) in the PFC or vHIP of rats affects neuronal oscillatory activity and leads to deficits in learning and memory. These changes are accompanied by aberrant phosphorylation of tau protein. Therefore, abnormal GSK-3 beta signaling may contribute to cognitive dysfunction disorders.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2022)
Article
Chemistry, Medicinal
Wenwu Liu, Xin Liu, Liting Tian, Yaping Gao, Wenjie Liu, Huanhua Chen, Xiaowen Jiang, Zihua Xu, Huaiwei Ding, Qingchun Zhao
Summary: Harmine derivatives were designed, synthesized, and evaluated as dual GSK-3 beta/DYRK1A inhibitors, showing promising activity against both targets. Compound ZDWX-25 exhibited potent inhibitory effects on GSK-3 beta and DYRK1A, with IC50 values of 71 and 103 nM, respectively. These compounds have the potential to be promising candidates for Alzheimer's disease treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Yuan Pan, Jared D. Hysinger, Tara Barron, Nicki F. Schindler, Olivia Cobb, Xiaofan Guo, Belgin Yalcin, Corina Anastasaki, Sara B. Mulinyawe, Anitha Ponnuswami, Suzanne Scheaffer, Yu Ma, Kun-Che Chang, Xin Xia, Joseph A. Toonen, James J. Lennon, Erin M. Gibson, John R. Huguenard, Linda M. Liau, Jeffrey L. Goldberg, Michelle Monje, David H. Gutmann
Summary: Neurons play an essential role in promoting the growth of certain types of brain tumors, such as optic pathway gliomas driven by mutations in the NF1 tumor suppressor gene. Inhibition of neuronal activity through light deprivation can prevent tumor formation and progression, highlighting a potential therapeutic strategy and the importance of Nf1 mutation-mediated dysregulation of neuronal signaling pathways in cancer predisposition syndromes.
Article
Engineering, Mechanical
Quanbao Ji, Xinxin Qie, Min Ye
Summary: This paper presents a computational model that explores integrated information in the bidirectional communication between neurons and astrocytes. The study analyzes the dynamics and information transfer process when stimulating metabotropic glutamate in coupled neuron and astrocyte models. The results demonstrate that the stimulation and coupling strength induce neuronal hyperexcitation, which is partially connected to epileptic instabilities. Additionally, the sustained firing activities of neurons can persist after stimulation cessation due to the time it takes for calcium concentration in astrocytes to reach a steady state. Furthermore, reducing astrocyte feedback effectively inhibits seizure-like firing in neurons from the perspective of neuronal energy consumption.
NONLINEAR DYNAMICS
(2023)
Article
Mathematics, Interdisciplinary Applications
Tugba Palabas, Joaquin J. Torres, Matjaz Perc, Muhammet Uzuntarla
Summary: An increasing amount of evidence suggests that astrocytes, an abundant type of glial cells in the nervous system, not only support neurons structurally and metabolically, but also modulate neuronal and synaptic functions. However, their role in information processing, especially in the presence of noise, remains unclear. This study investigates the phenomenon of stochastic resonance in neuronal dynamics and shows that astrocytes can enhance the detection of weak signals in the presence of noise, indicating their potential role in noisy neuronal information processing.
CHAOS SOLITONS & FRACTALS
(2023)
Article
Biochemistry & Molecular Biology
Jie Ai, Hongyan Wang, Peng Chu, Abdullah Shopit, Mengyue Niu, Nisar Ahmad, Tsehaye Tesfaldet, Fu Han Wang, Jia Ni Fang, Xiaodong Li, Shi Jie Tang, Qing Ju Han, Guozhu Han, Jinyong Peng, Zeyao Tang
Summary: The study demonstrates that phosphocreatine (PCr) can protect neuronal cells from A beta protein-induced injury through various pathways, such as reducing oxidative stress and apoptotic pathway activities, as well as modulating Tau protein phosphorylation and other key signaling pathways.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Neurosciences
Xiaoqian Peng, Hongsong Guo, Xiao Zhang, Zikang Yang, John Bosco Ruganzu, Zhuoyuan Yang, Xiangyuan Wu, Wei Bi, Shengfeng Ji, Weina Yang
Summary: This study found that TREM2 can inhibit tau hyperphosphorylation and neuronal apoptosis through the activation of the PI3K/Akt/GSK-3β signaling pathway, thereby improving Alzheimer's disease. This finding helps us better understand the protective role of TREM2 in tau pathology and provides new ideas and targets for the treatment of Alzheimer's disease.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yanwen Wang, Miao Cai, Yue Lou, Siran Zhang, Xiaoli Liu
Summary: The study demonstrated that the upregulation of LncRNA ZBTB20-AS1 suppressed the expression of ZBTB20 and promoted the expression of GSK-3 beta and phosphorylation of Tau, thus contributing to the development of Alzheimer's disease.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Zhongwen Luo, Shang Li, Yonglei Zhang, Fucheng Yin, Heng Luo, Xinye Chen, Ningjie Cui, Siyuan Wan, Xinxin Li, Lingyi Kong, Xiaobing Wang
Summary: Neuronal cells overexpressing phosphorylated Tau proteins increase susceptibility to oxidative stress. Regulation of GSK-3 beta and reduction of Tau protein hyperphosphorylation, as well as alleviation of oxidative stress, may be effective in preventing or treating Alzheimer's disease (AD). The compound KWLZ-9e showed potential GSK-3 beta inhibition and neuroprotective capacity, and it could alleviate oxidative stress and improve learning and memory impairments in an AD model, making it a promising lead for AD treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Clinical Neurology
Wei Zeng, Chunyuan Zhang, Qingshan Long, Yalan Li
Summary: This study found that dexmedetomidine can reverse the hippocampal neuron damage caused by lipopolysaccharide, including neurite outgrowth and synaptic transmission dysfunction. By activating the AKT/GSK-3β/CRMP-2 signaling pathway, dexmedetomidine can alleviate LPS-induced neurological dysfunction.
NEUROPSYCHIATRIC DISEASE AND TREATMENT
(2021)
Article
Cell Biology
Ena Spanic, Lea Langer Horvat, Katarina Ilic, Patrick R. Hof, Goran Simic
Summary: Neuroinflammation is a key pathological feature of Alzheimer's disease (AD). This study demonstrates that NLRP1 inflammasome is more active in the AD brain and is positively correlated with the number of neurofibrillary tangles (NFTs), suggesting a causal link between neuroinflammation and neurofibrillary degeneration.
Article
Multidisciplinary Sciences
Sivaprakasam R. Saroja, Kirill Gorbachev, T. C. W. Julia, Alison M. Goate, Ana C. Pereira
Summary: A protein called glypican-4 (GPC-4) secreted by astrocytes is shown to drive tau hyperphosphorylation induced by APOE4, a genetic risk factor for Alzheimer's disease. This discovery provides insights into the mechanisms underlying tauopathies and highlights the role of GPC-4 in tau accumulation and propagation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
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)
Article
Neurosciences
Yinhong Zhang, Jinghui Yang, Yanling Gong, Shan He, Ping Wen, Yan Jiang, Jing He, Baosheng Zhu, Li Li
Summary: This study investigated the effects of curcumin on the synaptic development of rat hippocampal neurons. It was found that curcumin increased the number of synapses and promoted neurodevelopment. The mechanism involved the inhibition of GSK-3 beta and protection of beta-catenin activity by curcumin. This alleviated oxidative damage caused by thyroxine deficiency.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Melanie Alpaugh, Helena L. Denis, Francesca Cicchetti
Summary: Current research accepts the theory that pathological proteins associated with neurodegenerative disorders behave similarly to prions. Protein misfolding and prion-like properties play significant roles in neurodegenerative disorders, influencing disease progression and potential therapeutic strategies.
MOLECULAR PSYCHIATRY
(2022)
Article
Biotechnology & Applied Microbiology
Melanie Alpaugh, Maria Masnata, Aurelie de Rus Jacquet, Eva Lepinay, Helena L. Denis, Martine Saint-Pierre, Peter Davies, Emmanuel Planel, Francesca Cicchetti
Summary: This study suggests that attenuating tau pathology could mitigate behavioral and molecular hallmarks associated with Huntington's disease.
Review
Cell Biology
Bianca Marchetti, Carmela Giachino, Cataldo Tirolo, Maria F. Serapide
Summary: This article discusses the multifunctional role of dopamine (DA) signaling in neuroendocrine-immune modulation and its involvement in Parkinson's disease (PD). The degeneration of DA nigrostriatal pathway in PD leads to the loss of substantia nigra pars compacta (SNpc) neurons and disruption of glial inflammatory networks. The article emphasizes the reciprocal modulation between DA and glial cells, as well as the impact of gene-environment interactions on PD vulnerability. Additionally, the article introduces the role of DA as an endogenous modulator in the regulation of oxidative stress and inflammation, and explores the potential application of DA receptor agonists as immune modifiers in the clinic.
Editorial Material
Cell & Tissue Engineering
Janelle Drouin-Ouellet
Summary: The major improvement in generating astrocytes from human fibroblasts will enhance our understanding of the impact of aging on astrocyte function and neurodegenerative disorders.
CELLULAR REPROGRAMMING
(2022)
Article
Cell & Tissue Engineering
Emilie M. Legault, Julie Bouquety, Janelle Drouin-Ouellet
Summary: Understanding CNS-associated neurological diseases is challenging due to limited access to patient brain tissue. However, induced pluripotent stem cell differentiation and direct neural reprogramming offer alternative approaches to generate neural cells for research purposes.
CELLULAR REPROGRAMMING
(2022)
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
Cell & Tissue Engineering
Janelle Drouin-Ouellet, Dan Li, Yuancheng Ryan Lu, Camila Vazquez Echegaray
Summary: The International Society for Stem Cell Research celebrated its 20th anniversary with a hybrid event that showcased impressive research and promoted collaboration between academia and industry. The event highlighted the significant advancements made in the field over the past two decades.
CELLULAR REPROGRAMMING
(2022)
Article
Cell & Tissue Engineering
Janelle Drouin-Ouellet, Emilie M. Legault, Fredrik Nilsson, Karolina Pircs, Julie Bouquety, Florence Petit, Shelby Shrigley, Marcella Birtele, Maria Pereira, Petter Storm, Yogita Sharma, Andreas Bruzelius, Romina Vuono, Malin Kele, Thomas B. Stoker, Daniella Rylander Ottosson, Anna Falk, Johan Jakobsson, Roger A. Barker, Malin Parmar
Summary: We have developed an efficient approach to generate functional induced dopaminergic neurons from adult human dermal fibroblasts and could specifically detect disease-relevant pathology in patient cells. These patient-derived neurons can serve as a cellular model to study age-related pathology relevant to Parkinson's disease.
Editorial Material
Neurosciences
Janelle Drouin-Ouellet
Summary: In this Journal Club, Janelle Drouin-Ouellet discusses a paper from 1989 that presented the initial evidence of mitochondrial dysfunction in individuals with idiopathic Parkinson's disease.
NATURE REVIEWS NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Maninder Heer, Luca Giudice, Claudia Mengoni, Rosalba Giugno, Daniel Rico
Summary: Researchers have developed a new method called Esearch3D to identify active enhancers using network theory approaches. This method calculates the likelihood of enhancer activity in intergenic regions by analyzing the folding of chromatin in the three-dimensional nuclear space, and regions predicted to have high enhancer activity are shown to be enriched in annotations indicative of enhancer activity.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Naomi I. Maria, Rosaria Valentina Rapicavoli, Salvatore Alaimo, Evelyne Bischof, Alessia Stasuzzo, Jantine A. C. Broek, Alfredo Pulvirenti, Bud Mishra, Ashley J. Duits, Alfredo Ferro, RxCOVEA Framework
Summary: The current pandemic has created an urgent need for identifying potential drugs for COVID-19. However, our understanding of the host-immune response to SARS-CoV-2 is limited, and there are only a few approved drugs available. To address this, a systems biology tool called PHENotype SIMulator has been introduced. This tool uses transcriptomic and proteomic databases to simulate SARS-CoV-2 infection in host cells, allowing for the identification of viral effects on host-immune response with high sensitivity and specificity (>96%).
Review
Biochemistry & Molecular Biology
Eva Lepinay, Francesca Cicchetti
Summary: Developing effective treatments for Huntington's disease is challenging, and finding robust biomarkers is crucial for diagnosis and treatment.
MOLECULAR PSYCHIATRY
(2023)
Article
Mathematical & Computational Biology
Eva Viesi, Davide Stefano Sardina, Ugo Perricone, Rosalba Giugno
Summary: The World Health Organization estimates that 9 out of 10 people worldwide breathe air containing high levels of pollutants, which can have detrimental effects on vital organs. In order to investigate the link between pollutant exposure and human health effects, the development of an online resource collecting and characterizing pollutant molecules could be beneficial. The APDB database was created to collect air-pollutant-related data from various online resources, including molecules, targets, bioassays, and computed properties. The database provides a web interface for browsing, querying, and visualizing the data.
DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION
(2023)
Article
Computer Science, Artificial Intelligence
Luca Gallo, Vito Latora, Alfredo Pulvirenti
Summary: Research on graph representation learning has been highly focused on single-layer graphs, and there is limited research on representation learning of multilayer structures without known inter-layer links. This study proposes MultiplexSAGE, a generalized algorithm capable of embedding multiplex networks and reconstructing intra-layer and inter-layer connectivity. Experimental analysis reveals that the quality of embedding is strongly influenced by the density and randomness of the graph's links in both simple and multiplex networks.
IEEE TRANSACTIONS ON NEURAL NETWORKS AND LEARNING SYSTEMS
(2023)
Article
Biology
Simone Avesani, Eva Viesi, Luca Alessandri, Giovanni Motterle, Vincenzo Bonnici, Marco Beccuti, Raffaele Calogero, Rosalba Giugno
Summary: In this study, a new clustering method called Stardust was proposed, which can easily utilize spatial and transcriptomic information to improve clustering analysis. By analyzing ST datasets, the method showed excellent performance in clustering.