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)
Review
Medicine, Research & Experimental
Jinrui Wei, Yan Zhang, Haopeng Li, Fuquan Wang, Shanglong Yao
Summary: This review focuses on the role and mechanism of TLR4 in various diseases, aiming to provide new research directions and therapeutic targets for clinical intervention.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Cell Biology
Lee Wei Lim, Md . Sahab Uddin
Summary: Alzheimer's disease is a neurodegenerative disorder with unclear pathogenesis. Recent research suggests that microglia and astrocytes may play a role in the development of AD and could be potential therapeutic targets.
AGEING RESEARCH REVIEWS
(2022)
Article
Pharmacology & Pharmacy
Lucia Yi-Ru Chung, Yi-Ting Lin, Chi Liu, Yi-Cheng Tai, Han-Yi Lin, Chin-Hsien Lin, Ching-Chow Chen
Summary: This study reveals that activated microglia-derived neuroinflammation induces neuronal TLR2/4-p38/JNK activation, disrupting autophagy and leading to accumulation of alpha-synuclein aggregates and neurite shortening. Targeting neuronal TLR2/4 pathway might provide a mechanistic-based therapy for neurodegenerative diseases such as Parkinson's disease.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Medicine, Research & Experimental
Ankush Kumar Jha, Shobhit Gairola, Sourav Kundu, Pakpi Doye, Abu Mohammad Syed, Chetan Ram, Upadhyayula Suryanarayana Murty, V. G. M. Naidu, Bidya Dhar Sahu
Summary: This review emphasizes the role of TLR4 signaling pathway in AKI and highlights potential compounds of natural and synthetic origin that can avert renal TLR4 signaling and offer protection against AKI in preclinical models. Targeting TLR4 and its downstream effectors could serve as an effective therapeutic intervention to prevent renal inflammation and subsequent kidney damage.
Article
Biochemistry & Molecular Biology
Nauana Somensi, Samantha Cristiane Lopes, Juciano Gasparotto, Rosangela Mayer Goncalves, Camila Tiefensee-Ribeiro, Daniel Oppermann Peixoto, Pedro Ozorio Brum, Cibele Martins Pinho, Jonathan Paulo Agnes, Lucas Santos, Jade de Oliveira, Fernando Spiller, Jose Claudio Fonseca Moreira, Alfeu Zanotto-Filho, Rui Daniel Prediger, Daniel Pens Gelain
Summary: This study found gender differences in the development of Parkinson's disease, with the knockout of TLR4 in female mice preventing dopaminergic denervation and microgliosis induced by 6-OHDA, leading to improvements in both non-motor and motor symptoms.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Review
Cell Biology
Bahareh Kashani, Zahra Zandi, Atieh Pourbagheri-Sigaroodi, Davood Bashash, Seyed H. Ghaffari
Summary: The TLR family is crucial for pattern recognition in innate immunity, with TLR4 playing a significant role in inflammatory diseases and cancer. Aberrant expression of TLR4 in tumors is closely associated with tumorigenesis, progression, and drug resistance. TLR4 inhibitors show promise in cancer therapy.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Noah Goshi, Hyehyun Kim, Erkin Seker
Summary: This study demonstrates the screening capabilities of a primary cortical cell tri-culture and emphasizes the significant role of microglia in the neuroinflammatory response to TLR activation in vitro.
Article
Biochemistry & Molecular Biology
Anna Piovan, Raffaella Filippini, Carla Argentini, Stefano Moro, Pietro Giusti, Morena Zusso
Summary: The blue-green alga Spirulina platensis contains phycocyanins, including C-phycocyanin (C-PC), which has hepatoprotective, nephroprotective, antioxidant, and anticancer effects. This study investigated the immunomodulatory effects of C-PC in microglia cultures and found that it upregulates the expression and release of IL-1 beta and TNF-alpha, while also promoting the nuclear translocation of the NF-kappa B transcription factor. Additionally, the study suggests that the immunoregulatory function of C-PC may involve the activation of Toll-like receptor 4 (TLR4).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Geriatrics & Gerontology
Qinqin Wang, Hongmei Yao, Wenyan Liu, Bailiu Ya, Hongju Cheng, Zhenkai Xing, Yili Wu
Summary: Microglia regulated neuroinflammation plays an important role in the pathogenesis of Alzheimer's disease (AD). M1 and M2 microglia have pro-inflammatory and anti-inflammatory effects, respectively, in AD. Aβ and hyperphosphorylated tau are implicated in microglial activation and subsequent inflammation, contributing to neuronal and synaptic loss in AD.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Immunology
Shiqi Zhou, Yanyan Li, Zhao Zhang, Yuhe Yuan
Summary: The TAM receptors may have a role in delaying the progression of Alzheimer's disease (AD), the most common neurodegenerative disease associated with aging. These receptors are associated with immune responses, cellular differentiation and migration, and clearance of apoptotic cells and debris. Research suggests that the TAM system is involved in AD pathology and regulates microglia, the key sensors of disorder in the central nervous system (CNS).
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Changliang Zhu, Hong Tao, Shikuo Rong, Lifei Xiao, Xinxiao Li, Shucai Jiang, Baorui Guo, Lei Wang, Jiangwei Ding, Caibing Gao, Haigang Chang, Tao Sun, Feng Wang
Summary: Exendin-4 was effective in inhibiting cocaine-induced CPP, facilitating the extinction of cocaine-associated reward, and attenuating reinstatement of cocaine-induced behavior. These effects may be attributed to the inhibition of TLR4, TNF-alpha, and IL-1 beta expression.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Neurosciences
Guimei Zhang, Zicheng Wang, Huiling Hu, Meng Zhao, Li Sun
Summary: Alzheimer's disease is a common type of age-related dementia, where dysregulated microglia activity can lead to chronic neuroinflammation, promote pathological protein accumulation, and impair mitophagy. Targeting microglia may offer new therapeutic interventions for the disease.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Immunology
Zhiyu Wang, Donald F. Weaver
Summary: Alzheimer's disease is a neurodegenerative disorder characterized by the progressive deterioration of multiple cognitive functions. Microglial cells play a crucial role in the pathogenesis of Alzheimer's disease through the recognition and response to misfolded proteins like beta-amyloid and tau. These proteins contribute to neuroinflammation and neurotoxicity, while microglia's primary function is to maintain brain homeostasis and synaptic integrity. However, prolonged activation of microglia can be harmful. This review discusses the role of microglia in Alzheimer's disease pathogenesis and explores potential drug candidates targeting microglial receptors.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Jacques Hugon, Claire Paquet
Summary: Neuropathological lesions in Alzheimer's disease involve amyloid plaques, neurofibrillary tangles, and neuroinflammation, potentially related to kinase activation. Clinical trials testing a p38 mitogen-activated protein kinase inhibitor have been unsuccessful, highlighting the importance of this pathway in AD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)