Lipocalin-2 as a mediator of neuroimmune communication.

Lipocalin-2, a neutrophil gelatinase-associated lipocalin, is a 25-kDa secreted protein implicated in a broad range of inflammatory diseases affecting the brain and periphery. It is a pleotropic protein expressed by various immune and nonimmune cells throughout the body. Importantly, the surge in lipocalin-2 levels in disease states has been associated with a myriad of undesirable effects, further exacerbating the ongoing pathological processes.

Utilizing databases for astrocyte secretome research.

Introduction: Astrocytes are the most abundant cell type in the central nervous system (CNS). They play a pivotal role in supporting neuronal function and maintaining homeostasis by releasing a variety of bioactive proteins, collectively known as the astrocyte secretome. Investigating secretome provides insights into the molecular mechanisms underlying astrocyte function and dysfunction, as well as novel strategies to prevent and treat diseases affecting the CNS.

Analyzing the glial proteome in Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, memory loss, and changes in behavior. Accumulating evidence indicates that dysfunction of glial cells, including astrocytes, microglia, and oligodendrocytes, may contribute to the development and progression of AD. Large-scale analysis of glial proteins sheds light on their roles in cellular processes and diseases.

Microglial Responses to Stress-Induced Depression: Causes and Consequences.

Chronic stress is a major risk factor for various psychiatric diseases, including depression; it triggers various cellular and structural changes, resulting in the alteration of neurocircuitry and subsequent development of depression. Accumulating evidence suggests that microglial cells orchestrate stress-induced depression. Preclinical studies of stress-induced depression revealed microglial inflammatory activation in regions of the brain that regulate mood.

A multiplexed siRNA screen identifies key kinase signaling networks of brain glia.

The dynamic behaviors of brain glial cells in various neuroinflammatory conditions and neurological disorders have been reported; however, little is known about the underlying intracellular signaling pathways. Here, we developed a multiplexed kinome-wide siRNA screen to identify the kinases regulating several inflammatory phenotypes of mouse glial cells in culture, including inflammatory activation, migration, and phagocytosis of glia. Subsequent proof-of-concept experiments involving genetic and pharmacological inhibitions indicated the importance of T-cell receptor signaling components in microglial activation and a metabolic shift from glycolysis to oxidative phosphorylation in astrocyte migration.

Bidirectional Communication Between Microglia and Astrocytes in Neuroinflammation.

Neuroinflammation is a common feature of diverse nervous system pathologies. In many instances, it begins at an early stage of the disease, paving the way for further exacerbations. The main drivers of neuroinflammation are brain-resident glial cells, such as microglia and astrocytes.

Soluble ANPEP Released From Human Astrocytes as a Positive Regulator of Microglial Activation and Neuroinflammation: Brain Renin-Angiotensin System in Astrocyte-Microglia Crosstalk.

Astrocytes are major supportive glia and immune modulators in the brain; they are highly secretory in nature and interact with other cell types via their secreted proteomes. To understand how astrocytes communicate during neuroinflammation, we profiled the secretome of human astrocytes following stimulation with proinflammatory factors. A total of 149 proteins were significantly upregulated in stimulated astrocytes, and a bioinformatics analysis of the astrocyte secretome revealed that the brain renin-angiotensin system (RAS) is an important mechanism of astrocyte communication.

Implications of glial metabolic dysregulation in the pathophysiology of neurodegenerative diseases.

Glial cells are the most abundant cells of the brain, outnumbering neurons. These multifunctional cells are crucial for maintaining brain homeostasis by providing trophic and nutritional support to neurons, sculpting synapses, and providing an immune defense. Glia are highly plastic and undergo both structural and functional alterations in response to changes in the brain microenvironment.

The Function of Glial Cells in the Neuroinflammatory and Neuroimmunological Responses.

The historical concept of glia just as the glue of brain tissue has been challenged by the accumulation of concrete evidence showing the multifunctional role of these cells during development and in the adult brain [...

Neuroinflammatory Basis of Depression: Learning From Experimental Models.

The neuroinflammatory basis of depression encompasses the detrimental role of otherwise supportive non-neuronal cells and neuroinflammation in hampering neuronal function, leading to depressive behavior. Animals subjected to different stress paradigms show glial cell activation and a surge in proinflammatory cytokines in various brain regions. The concept of sterile inflammation observed in animal models of depression has intrigued many researchers to determine the possible triggers of central immune cell activation.

Brain-immune interactions in neuropsychiatric disorders: Lessons from transcriptome studies for molecular targeting.

Understanding the pathophysiological mechanisms of neuropsychiatric disorders has been a challenging quest for neurobiologists. Recent years have witnessed enormous technological advances in the field of neuroimmunology, blurring boundaries between the central nervous system and the periphery. Consequently, the discipline has expanded to cover interactions between the nervous and immune systems in health and diseases.

Gamma subunit of complement component 8 is a neuroinflammation inhibitor.

The complement system is part of the innate immune system that comprises several small proteins activated by sequential cleavages. The majority of these complement components, such as components 3a (C3a) and C5a, are chemotactic and pro-inflammatory. However, in this study, we revealed an inhibitory role of complement component 8 gamma (C8G) in neuroinflammation.

Selection, purification, and evaluation of acarbose-an α-glucosidase inhibitor from Actinoplanes sp.

Actinoplanes sp. A1094 strain had been selected for its high production of acarbose from 20 different strains of Actinoplanes sp. can be found in wild.

Microglia Gone Awry: Linking Immunometabolism to Neurodegeneration.

Age-related chronic inflammatory activation of microglia and their dysfunction are observed in many neurodegenerative diseases, and the potential contributions of these dysfunctional cells to neurodegeneration have been demonstrated recently. The housekeeping and defensive functions of microglia, such as surveying the brain parenchyma and phagocytosis of neuronal debris after injury, are important for brain homeostasis and immunity. During neurodegenerative diseases, loss of these functions can promote disease pathology by producing proinflammatory cytokines and increasing oxidative stress, which can exaggerate the ongoing neuroinflammation.

Proteomic examination of the neuroglial secretome: lessons for the clinic.

: Glial cells are closely associated with neurons located throughout the nervous system and regulate neuronal activity and function through various mechanisms including the secretion of proteins and other signaling molecules. Glia-secreted proteins play crucial roles in modulating neuronal function in physiological and pathological conditions. Aberrant activation of glial cells leading to neuroinflammation is a common phenomenon observed in various neurological disorders.

Metabolic Regulation of Glial Phenotypes: Implications in Neuron-Glia Interactions and Neurological Disorders.

Glial cells are multifunctional, non-neuronal components of the central nervous system with diverse phenotypes that have gained much attention for their close involvement in neuroinflammation and neurodegenerative diseases. Glial phenotypes are primarily characterized by their structural and functional changes in response to various stimuli, which can be either neuroprotective or neurotoxic. The reliance of neurons on glial cells is essential to fulfill the energy demands of the brain for its proper functioning.

Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in mice.

Background: Poncirin is flavanone derivative (isolated from Poncirus trifoliata) with known pharmacological activities such as anti-tumor, anti-osteoporotic, anti-inflammatory and anti-colitic. The present study aimed to explore the anti-allodynic and anti-hyperalgesic potentials of poncirin in murine models of inflammatory pain.

Methods: The analgesic potential of poncirin was evaluated in formalin-, acetic acid-, carrageenan- and Complete Freund's Adjuvant (CFA)-induced inflammatory pain models in mice.

Antinociceptive properties of 25-methoxy hispidol A, a triterpinoid isolated from Poncirus trifoliata (Rutaceae) through inhibition of NF-κB signalling in mice.

The 25-methoxy hispidol A (25-MHA) is a triterpenoid, isolated from the immature fruit of Poncirus trifoliata (Rutaceae). The pretreatment with 25-MHA markedly (p < 0.001) attenuated the formalin-induced biphasic responses as well as acetic acid-induced writhing responses.

Attenuation of inflammatory pain by puerarin in animal model of inflammation through inhibition of pro-inflammatory mediators.

In the current study, the puerarin was investigated for both acute Carrageenan and chronic CFA-induced inflammatory pain models. The Puerarin treatment significantly attenuated (P < 0.001) the mechanical hyperalgesia and mechanical allodynia in both Carrageenan and CFA-induced hyperalgesia.

Antihyperalgesic Properties of Honokiol in Inflammatory Pain Models by Targeting of NF-κB and Nrf2 Signaling.

The present study investigates the possible anti-nociceptive effect of intraperitoneal (i.p.) honokiol: a phenolic compound originally isolated from , in acute and chronic inflammatory pain models.