Article
Neurosciences
Houmin Lin, Steven Grant Dixon, Wei Hu, Eric D. Hamlett, Junfei Jin, Adviye Ergul, Gavin Y. Wang
Summary: Research suggests that the accumulation of amyloid beta (Aβ) plaques in the brain is a key factor in the development of Alzheimer's disease (AD). This study found that Aβ(1-40) oligomers stimulate the expression of IL-6 in human microglial cells. The activation of p38 MAPK is associated with this increase in IL-6. Inhibition of p38 MAPK can prevent Aβ-induced IL-6 production. These findings indicate that targeting p38 MAPK could be a potential approach to reduce neuroinflammation caused by Aβ accumulation in AD.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yanqing Chen, Zhen Liu, Ping Gong, Haibo Zhang, Yijun Chen, Songquan Yao, Wei Li, Yan Zhang, Yang Yu
Summary: The chemerin/CMKLR1 axis is involved in the migration and recruitment of microglia to senile plaques via the p38 MAPK pathway. Activation of the chemerin/CMKLR1 axis promotes microglial polarization and protrusion formation, and regulates microglial migration and clustering through the p38 MAPK pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Haidong Xu, Xiaolei Liu, Wenming Li, Ye Xi, Peng Su, Bo Meng, Xiaoyun Shao, Beisha Tang, Qian Yang, Zixu Mao
Summary: Dysregulation of miRNAs and reduced levels of Drosha protein in neurons, specifically in the cortex and hippocampus of AD brains, indicate a potential role in the pathogenesis of Alzheimer's disease. The phosphorylation of Drosha by p38 MAPK under A beta oligomers stress condition leads to neuronal apoptosis, highlighting the importance of the p38 MAPK-Drosha pathway in modulating neuronal viability.
Article
Neurosciences
Thomas J. LaRocca, Alyssa N. Cavalier, Christine M. Roberts, Maddie R. Lemieux, Pooja Ramesh, Micklaus A. Garcia, Christopher D. Link
Summary: The amyloid beta (A beta) peptide is believed to have a central role in Alzheimer's disease by synergistically promoting pro-inflammatory activation in primary human astrocytes with known cytokines. By directly substituting for the complement component C1q in a cytokine cocktail, A beta activates astrocytes similarly to neurotoxic astrocytes found in brain aging and AD. The biological action of A beta at low concentrations is distinct from that of high doses typically used in in vitro studies.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Alice Filippini, Valentina Salvi, Vincenzo Dattilo, Chiara Magri, Stefania Castrezzati, Robert Veerhuis, Daniela Bosisio, Massimo Gennarelli, Isabella Russo
Summary: The accumulation of amyloid-beta in Alzheimer's disease (AD) brains causes reactive astrogliosis and neuroinflammatory response. This study investigates the role of leucine-rich repeat kinase 2 (LRRK2) in regulating astrocytic activation in response to amyloid-beta(1-42) (A beta(1-42)). The results demonstrate that LRRK2 kinase activity modulates astrocytic reactivity and functions in the presence of A beta(1-42) deposits, suggesting a potential contribution of PD-linked LRRK2 to AD-related neuroinflammation and pathogenesis.
Article
Clinical Neurology
Nicola Spotorno, Olof Strandberg, Geraline Vis, Erik Stomrud, Markus Nilsson, Oskar Hansson
Summary: Metrics of cortical microstructural alteration derived from diffusion MRI are highly sensitive to multiple aspects of the Alzheimer's disease pathological cascade, particularly the associations with Aβ-PET and GFAP, making them important outcome measures in clinical trials for disease-modifying therapies.
Review
Immunology
Deepali Singh
Summary: Neuroinflammation is caused by the misfiring of immune cells in the central nervous system and can have both positive and negative effects on neurodevelopment and post-injury tissue. Chronic or uncontrolled inflammatory responses may lead to neurodegenerative diseases, while abnormal activation of glial cells can mediate neuroinflammation.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Clinical Neurology
Shuntaro Natsume, Hajime Baba, Hitoshi Maeshima, Takao Saida, Naoto Yoshinari, Kentaro Shimizu, Toshihito Suzuki
Summary: Depression is a risk factor for Alzheimer's disease, and changes in A13 protein metabolism may contribute to the transition from depression to AD. This study found that elderly patients with depression had decreased A1342 levels at admission, but these levels recovered to healthy levels 1 year after remission.
JOURNAL OF AFFECTIVE DISORDERS
(2022)
Article
Cell Biology
Shuqi Du, Feng Jin, Laure Maneix, Manasee Gedam, Yin Xu, Andre Catic, Meng C. Wang, Hui Zheng
Summary: This study reveals a specific regulation of FoxO3 in the CNS, showing reduced levels in the cortex of aged mice but not in the hippocampus. FoxO3 responds to insulin/AKT signaling in astrocytes and plays a role in astrocyte activity and lipid metabolism. Loss of FoxO3 leads to cortical astrogliosis, altered lipid metabolism, and impaired A beta uptake, indicating a protective role of astroglial FoxO3 against brain aging and AD.
Article
Immunology
Evangelos Konstantinidis, Benjamin Portal, Tobias Mothes, Chiara Beretta, Maria Lindskog, Anna Erlandsson
Summary: This study reveals that astrocytes in Alzheimer's disease (AD) are not only associated with the pathology but also play a crucial role in maintaining brain homeostasis and synaptic function. The accumulation of aggregated amyloid-beta (A beta) in astrocytes affects their interaction with neurons, leading to synaptic dysfunction and neuronal apoptosis. These findings are important for understanding the involvement of astrocytes in AD-related synaptic dysfunction.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Clinical Neurology
Amy M. Smith, Karen Davey, Stergios Tsartsalis, Combiz Khozoie, Nurun Fancy, See Swee Tang, Eirini Liaptsi, Maria Weinert, Aisling McGarry, Robert C. J. Muirhead, Steve Gentleman, David R. Owen, Paul M. Matthews
Summary: The study reveals significant differences in gene expression in astrocytes and microglia in the brains of AD patients, correlated with amyloid-beta or pTau expression. There are distinct gene expression patterns in the two cell types and pathologies, but common gene sets exist in each cell type. Additionally, different sub-clusters are found in astrocytes and microglia, characterized by transcriptional signatures related to either homeostatic functions or disease pathology.
ACTA NEUROPATHOLOGICA
(2022)
Article
Immunology
Dorit Farfara, Meital Sooliman, Limor Avrahami, Tabitha Grace Royal, Shoshik Amram, Lea Rozenstein-Tsalkovich, Dorit Trudler, Shani Blanga-Kanfi, Hagit Eldar-Finkelman, Jens Pahnke, Hanna Rosenmann, Dan Frenkel
Summary: In this study, researchers generated a new mouse model by crossing different mutant mouse models and found that the expression of the TAU gene in astrocytes in the 5xFAD TAU mice exacerbates AD. This suggests the role of TAU in exacerbating Aβ pathology and highlights the potential role of astrocytes in disease progression.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Biochemistry & Molecular Biology
Elena V. V. Mitroshina, Alexander M. M. Pakhomov, Mikhail I. I. Krivonosov, Roman S. S. Yarkov, Maria S. S. Gavrish, Alexey V. V. Shkirin, Mikhail V. V. Ivanchenko, Maria V. V. Vedunova
Summary: This study investigates the impact of astrocytes on the calcium activity of neuron-astroglia networks in Alzheimer's disease (AD) modeling. The researchers developed an algorithm to analyze the dynamic directed graphs of both astrocytic and neuronal networks, allowing them to identify functional relationships and characterize the spread of calcium signal. The study found that Alzheimer's astrocytes can alter the functional pattern of calcium activity in healthy nerve cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Raquel Sanchez-Varo, Marina Mejias-Ortega, Juan Jose Fernandez-Valenzuela, Cristina Nunez-Diaz, Laura Caceres-Palomo, Laura Vegas-Gomez, Elisabeth Sanchez-Mejias, Laura Trujillo-Estrada, Juan Antonio Garcia-Leon, Ines Moreno-Gonzalez, Marisa Vizuete, Javier Vitorica, David Baglietto-Vargas, Antonia Gutierrez
Summary: This review provides an overview of the major pathological elements of Alzheimer's disease and discusses the insights provided by mouse models in understanding the underlying mechanisms. It highlights the pros and cons of current models and explores the potential benefits of combining transgenic mice with omics technologies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Maria Olmedillas, Bianca Brawek, Kaizhen Li, Cris Richter, Olga Garaschuk
Summary: Microglia, the major immune cells of the brain, display both mobility and low turnover in healthy adult mice but undergo increased division and death rates in Alzheimer's disease with amyloid deposition. Despite amyloid plaques becoming the major destination of migration, the basic migration properties of microglia remain preserved, with a significant association with blood vessels. The plaque vicinity becomes a hotspot for microglial turnover, harboring the majority of migration, death, and division events.