Article
Neurosciences
Natalia Salvadores, Ines Moreno-Gonzalez, Nazaret Gamez, Gabriel Quiroz, Laura Vegas-Gomez, Marcela Escandon, Sebastian Jimenez, Javier Vitorica, Antonia Gutierrez, Claudio Soto, Felipe A. Court
Summary: Alzheimer's disease is a neurodegenerative condition with no available treatment. Amyloid-beta is identified as the main cause of the disease, and its burden correlates with markers of necroptosis activation. Inhibition of necroptosis reduces neurodegeneration and memory impairment caused by amyloid-beta. Activation of TNF-alpha signaling in neurons by amyloid-beta-stimulated microglia triggers extensive neurodegeneration, which can be protected by inhibiting necroptosis.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Review
Geriatrics & Gerontology
Guy C. Brown, Peter St George-Hyslop
Summary: TREM2 is a pattern recognition receptor expressed on myeloid cells that plays a crucial role in Alzheimer's disease. Soluble TREM2 (sTREM2) has a protective effect by blocking Aβ fibrillization and neurotoxicity. Higher levels of sTREM2 are associated with slower progression of AD.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Yasuteru Inoue, Masayoshi Tasaki, Teruaki Masuda, Yohei Misumi, Toshiya Nomura, Yukio Ando, Mitsuharu Ueda
Summary: In this study, the researchers found that α-enolase (ENO1) can interact with amyloid beta (Aβ) and inhibit its fibril formation. They also demonstrated that ENO1 can disrupt Aβ fibrils and weaken their cytotoxic effects by degrading Aβ peptides. Additionally, infusion of ENO1 into mouse brains reduced cerebrovascular Aβ deposits and improved cognitive impairment. These findings suggest that ENO1 may be a therapeutic target in cerebral amyloid angiopathy (CAA).
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Yuanxin Zhao, Buhan Liu, Jian Wang, Long Xu, Sihang Yu, Jiaying Fu, Xiaoyu Yan, Jing Su
Summary: Neuroinflammation mediated by microglia is a common feature in neurodegenerative diseases. The accumulation of Aβ and tau proteins can disrupt the metabolism of microglia, leading to neuroinflammation.
Article
Multidisciplinary Sciences
Hannah Ennerfelt, Coco Holliday, Daniel A. Shapiro, Kristine E. Zengeler, Ashley C. Bolte, Tyler K. Ulland, John R. Lukens
Summary: Recent advances have shown the importance of microglia-expressed innate immune receptors in Alzheimer's disease (AD), specifically TREM2, CD33, and CD22. However, the downstream signaling molecules used by these receptors in AD are still not well understood. This study demonstrates that CARD9, an intracellular adaptor molecule, plays a crucial role in A(3-mediated disease and microglial responses in AD.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Kathleen M. Schoch, Lubov A. Ezerskiy, Michaela M. Morhaus, Riley N. Bannon, Andrew D. Sauerbeck, Mark Shabsovich, Paymaan Jafar-nejad, Frank Rigo, Timothy M. Miller
Summary: The study found that transient reduction of Trem2 messenger RNA levels in APP/PS1 mice significantly reduced plaque deposition and attenuated microglial association around plaques. The results suggest that Trem2 reduction may activate microglia and aid in plaque removal.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Geriatrics & Gerontology
Pei Ou-Yang, Zhi-Yu Cai, Zhong-Hao Zhang
Summary: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by protein aggregates, neuronal loss, synaptic dysfunction, and neuroinflammation. Impaired microglial autophagy has been shown to contribute to AD pathology by affecting inflammatory response, defective clearance, propagation of A beta and Tau, and synaptic dysfunction. Microglial receptors play a key role in regulating autophagy during AD. Inducing microglial autophagy shows potential as a strategy for AD drug development, based on accumulating evidence.
Article
Clinical Neurology
Rebecca L. Winfree, Mabel Seto, Logan Dumitrescu, Vilas Menon, Philip De Jager, Yanling Wang, Julie Schneider, David A. Bennett, Angela L. Jefferson, Timothy J. Hohman
Summary: This study investigated the correlation between region-specific TREM2 mRNA expression and neuropathology measures in a large sample size. The results showed that TREM2 expression was related to Alzheimer's disease pathology, cerebrovascular pathology, microglial activation, and cognitive decline, but the associations varied across different brain regions. These findings suggest that TREM2's pathological associations are dependent on the brain region.
ACTA NEUROPATHOLOGICA
(2023)
Article
Pharmacology & Pharmacy
Samuel Ruiz de Martin Esteban, Irene Benito-Cuesta, Itziar Terradillos, Ana M. Martinez-Relimpio, M. Andrea Arnanz, Gonzalo Ruiz-Perez, Claudia Korn, Catarina Raposo, Roman C. Sarott, Matthias V. Westphal, Izaskun Elezgarai, Erick M. Carreira, Cecilia J. Hillard, Uwe Grether, Pedro Grandes, M. Teresa Grande, Julian Romero
Summary: The cannabinoid CB2 receptors are found to be significantly elevated in chronic neuroinflammatory states associated with neurodegenerative diseases such as Alzheimer's disease, suggesting a potential therapeutic target in modulating amyloid metabolism through microglial CB2 receptors.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Plant Sciences
Min-Ji Jung, Namkwon Kim, Seung Ho Jeon, Min Sung Gee, Ji-Woon Kim, Jong Kil Lee
Summary: The study investigated the effects of eugenol on Alzheimer's disease (AD) and found that eugenol effectively improved cognitive function and reduced pathological changes in 5xFAD mice. The underlying mechanisms may involve inhibiting neuronal cell death and promoting beta-amyloid clearance.
Article
Biochemistry & Molecular Biology
Sareer Ahmad, Myeung Hoon Jo, Muhammad Ikram, Amjad Khan, Myeong Ok Kim
Summary: The study revealed that Luteolin has protective effects against amyloid-beta-induced neuroinflammation, amyloidogenesis, and synaptic dysfunction in mice, potentially through inhibition of JNK signaling and modulation of inflammatory and cell death markers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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
Cell Biology
Zhen Xie, Jie Meng, Wei Kong, Zhou Wu, Fei Lan, Narengaowa, Yoshinori Hayashi, Qinghu Yang, Zhantao Bai, Hiroshi Nakanishi, Hong Qing, Junjun Ni
Summary: The regulation of neuroinflammation and beta-amyloid production is important in the development of Alzheimer's disease. In this study, it was found that the elimination of CatE significantly reduced A beta accumulation, neuroinflammation, and cognitive impairments. The findings suggest that CatE may be a therapeutic target for Alzheimer's disease.
Article
Neurosciences
Anja Pislar, Biljana Bozic Nedeljkovic, Mina Peric, Tanja Jakos, Nace Zidar, Janko Kos
Summary: This study found that simultaneous activation of TLR3 and TLR4 induces synergistic microglial responses and affects cathepsin X expression and activity. Enhanced cathepsin X leads to inflammation-induced neurodegeneration, making it a potential therapeutic target for neurodegenerative diseases associated with excess inflammation.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Daniel C. Ellwanger, Shoutang Wang, Simone Brioschi, Zhifei Shao, Lydia Green, Ryan Case, Daniel Yoo, Dawn Weishuhn, Palaniswami Rathanaswami, Jodi Bradley, Sara Rao, Diana Cha, Peng Luan, Shilpa Sambashivan, Susan Gilfillan, Samuel A. Hasson, Ian N. Foltz, Menno van Lookeren Campagne, Marco Colonna
Summary: TREM2 plays a critical role in microglia activation trajectories, with ligand engagement being essential for certain activation pathways. Activation trajectories induced by stimuli are more prominent in female mice than male mice. Injection of hT2AB can replenish depleted microglial pools lacking certain activation trajectories.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)