Brain organoid models for studying the function of iPSC-derived microglia in neurodegeneration and brain tumours.

Microglia represent the main resident immune cells of the brain. The interplay between microglia and other cells in the central nervous system, such as neurons or other glial cells, influences the function and ability of microglia to respond to various stimuli. These cellular communications, when disrupted, can affect the structure and function of the brain, and the initiation and progression of neurodegenerative diseases including Alzheimer's disease and Parkinson's disease, as well as the progression of other brain diseases like glioblastoma.

The link between amyloid β and ferroptosis pathway in Alzheimer's disease progression.

Alzheimer's disease (AD) affects millions of people worldwide and represents the most prevalent form of dementia. Treatment strategies aiming to interfere with the formation of amyloid β (Aβ) plaques and neurofibrillary tangles (NFTs), the two major AD hallmarks, have shown modest or no effect. Recent evidence suggests that ferroptosis, a type of programmed cell death caused by iron accumulation and lipid peroxidation, contributes to AD pathogenesis.

Diesel exhaust particles alter mitochondrial bioenergetics and cAMP producing capacity in human bronchial epithelial cells.

Air pollution from diesel combustion is linked in part to the generation of diesel exhaust particles (DEP). DEP exposure induces various processes, including inflammation and oxidative stress, which ultimately contribute to a decline in lung function. Cyclic AMP (cAMP) signaling is critical for lung homeostasis.

Novel SK channel positive modulators prevent ferroptosis and excitotoxicity in neuronal cells.

Small conductance calcium-activated potassium (SK) channel activity has been proposed to play a role in the pathology of several neurological diseases. Besides regulating plasma membrane excitability, SK channel activation provides neuroprotection against ferroptotic cell death by reducing mitochondrial Ca uptake and reactive oxygen species (ROS). In this study, we employed a multifaceted approach, integrating structure-based and computational techniques, to strategically design and synthesize an innovative class of potent small-molecule SK2 channel modifiers through highly efficient multicomponent reactions (MCRs).

Negative modulation of mitochondrial calcium uniporter complex protects neurons against ferroptosis.

Ferroptosis is an iron- and reactive oxygen species (ROS)-dependent form of regulated cell death, that has been implicated in Alzheimer's disease and Parkinson's disease. Inhibition of cystine/glutamate antiporter could lead to mitochondrial fragmentation, mitochondrial calcium ([Ca]) overload, increased mitochondrial ROS production, disruption of the mitochondrial membrane potential (ΔΨ), and ferroptotic cell death. The observation that mitochondrial dysfunction is a characteristic of ferroptosis makes preservation of mitochondrial function a potential therapeutic option for diseases associated with ferroptotic cell death.

Lipid profile in breast cancer: From signaling pathways to treatment strategies.

Breast cancer is the most prevalent cancer in women. Metabolic abnormalities, particularly increased lipid synthesis and uptake, impact the onset and progression of the disease. However, the influence of lipid metabolism in breast cancer varies according to the disease stage and patient's hormone status.

Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction.

Metabolic reprogramming is a hallmark of the immune cells in response to inflammatory stimuli. This metabolic process involves a switch from oxidative phosphorylation (OXPHOS) to glycolysis or alterations in other metabolic pathways. However, most of the experimental findings have been acquired in murine immune cells, and little is known about the metabolic reprogramming of human microglia.

Mitochondrial transplantation rescues neuronal cells from ferroptosis.

Ferroptosis is a type of oxidative cell death that can occur in neurodegenerative diseases and involves damage to mitochondria. Previous studies demonstrated that preventing mitochondrial dysfunction can rescue cells from ferroptotic cell death. However, the complexity of mitochondrial dysfunction and the timing of therapeutic interventions make it difficult to develop an effective treatment strategy against ferroptosis in neurodegeneration conditions.

Characterization of Lipopolysaccharide Effects on LRRK2 Signaling in RAW Macrophages.

Dysfunction of the immune system and mitochondrial metabolism has been associated with Parkinson's disease (PD) pathology. Mutations and increased kinase activity of leucine-rich repeat kinase 2 (LRRK2) are linked to both idiopathic and familial PD. However, the function of LRRK2 in the immune cells under inflammatory conditions is contradictory.

Mitochondrial dysfunction mediates neuronal cell response to DMMB photodynamic therapy.

Photodynamic therapy (PDT) is a process in which a photosensitizer (PS) is exposed to specific wavelengths and generates reactive oxygen species (ROS) which act within nanometers. The low invasive nature and directed cytotoxicity of this approach render it attractive to the treatment of different conditions, including the ones that affect the central nervous system (CNS). The effect of PDT on healthy neurons is one main concern over its use in the CNS, since neuronal-like cells were shown to be particularly sensitive to certain PSs.

LRRK2 protects immune cells against erastin-induced ferroptosis.

Ferroptosis is an iron-dependent regulated cell death pathway characterized by excessive lipid peroxidation. It is implicated in many neurodegenerative diseases, including Parkinson's Disease (PD). Mutations and increased leucine-rich repeat kinase 2 (LRRK2) kinase activity are associated with both familial and idiopathic PD pathology.

Chemical structure and biological activity of the (1 → 3)-linked β-D-glucan isolated from marine diatom Conticribra weissflogii.

Several polysaccharides are considered to be "biological response modifiers" (BRM) - these refer to biomolecules that augment immune responses and can be derived from a variety of sources. Microalgae produce a diverse range of polysaccharides and could be an excellent source of BRM. Here, we describe the chemical structure and biological activity of water-soluble polysaccharide isolated from the marine diatom Conticribra weissflogii.

The Unfolded Protein Response Sensor PERK Mediates Stiffness-Dependent Adaptation in Glioblastoma Cells.

Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults. In addition to genetic causes, the tumor microenvironment (TME), including stiffening of the extracellular matrix (ECM), is a main driver of GBM progression. Mechano-transduction and the unfolded protein response (UPR) are essential for tumor-cell adaptation to harsh TME conditions.

Pharmacological Inhibition of Epac1 Averts Ferroptosis Cell Death by Preserving Mitochondrial Integrity.

Exchange proteins directly activated by cAMP (Epac) proteins are implicated in a wide range of cellular functions including oxidative stress and cell survival. Mitochondrial-dependent oxidative stress has been associated with progressive neuronal death underlying the pathology of many neurodegenerative diseases. The role of Epac modulation in neuronal cells in relation to cell survival and death, as well as its potential effect on mitochondrial function, is not well established.

Extracellular Matrix Proteome Remodeling in Human Glioblastoma and Medulloblastoma.

Medulloblastomas (MBs) and glioblastomas (GBMs) are high-incidence central nervous system tumors. Different origin sites and changes in the tissue microenvironment have been associated with the onset and progression. Here, we describe differences between the extracellular matrix (ECM) signatures of these tumors.

Low RECK Expression Is Part of the Cervical Carcinogenesis Mechanisms.

Human papillomavirus (HPV)-induced carcinogenesis comprises alterations in the expression and activity of matrix metalloproteinases (MMP) and their regulators. Reversion-inducing Cysteine-rich protein with Kazal motifs (RECK) inhibits the activation of specific metalloproteinases and its expression is frequently lost in human cancers. Here we analyzed the role of RECK in cervical carcinogenesis.

Glutaminolysis dynamics during astrocytoma progression correlates with tumor aggressiveness.

Background: Glioblastoma is the most frequent and high-grade adult malignant central nervous system tumor. The prognosis is still poor despite the use of combined therapy involving maximal surgical resection, radiotherapy, and chemotherapy. Metabolic reprogramming currently is recognized as one of the hallmarks of cancer.

Impact of Reck expression and promoter activity in neuronal in vitro differentiation.

Reck (REversion-inducing Cysteine-rich protein with Kazal motifs) tumor suppressor gene encodes a multifunctional glycoprotein which inhibits the activity of several matrix metalloproteinases (MMPs), and has the ability to modulate the Notch and canonical Wnt pathways. Reck-deficient neuro-progenitor cells undergo precocious differentiation; however, modulation of Reck expression during progression of the neuronal differentiation process is yet to be characterized. In the present study, we demonstrate that Reck expression levels are increased during in vitro neuronal differentiation of PC12 pheochromocytoma cells and P19 murine teratocarcinoma cells and characterize mouse Reck promoter activity during this process.

Mitochondrial dysfunction in neurodegenerative diseases: A focus on iPSC-derived neuronal models.

Progressive neuronal loss is a hallmark of many neurodegenerative diseases, including Alzheimer's and Parkinson's disease. These pathologies exhibit clear signs of inflammation, mitochondrial dysfunction, calcium deregulation, and accumulation of aggregated or misfolded proteins. Over the last decades, a tremendous research effort has contributed to define some of the pathological mechanisms underlying neurodegenerative processes in these complex brain neurodegenerative disorders.

Late p65 nuclear translocation in glioblastoma cells indicates non-canonical TLR4 signaling and activation of DNA repair genes.

Glioblastoma (GBM) is the most aggressive brain primary malignancy. Toll-like receptor 4 (TLR4) has a dual role in cell fate, promoting cell survival or death depending on the context. Here, we analyzed TLR4 expression in different grades of astrocytoma, and observed increased expression in tumors, mainly in GBM, compared to non-neoplastic brain tissue.

Calcium-activated potassium channels: implications for aging and age-related neurodegeneration.

Population aging, as well as the handling of age-associated diseases, is a worldwide increasing concern. Among them, Alzheimer's disease stands out as the major cause of dementia culminating in full dependence on other people for basic functions. However, despite numerous efforts, in the last decades, there was no new approved therapeutic drug for the treatment of the disease.

A-Kinase Anchoring Proteins Diminish TGF-β/Cigarette Smoke-Induced Epithelial-To-Mesenchymal Transition.

Epithelial-to-mesenchymal transition (EMT) plays a role in chronic obstructive pulmonary diseases (COPD). Cyclic adenosine monophosphate (cAMP) can inhibit transforming growth factor-β1 (TGF-β1) mediated EMT. Although compartmentalization via A-kinase anchoring proteins (AKAPs) is central to cAMP signaling, functional studies regarding their therapeutic value in the lung EMT process are lacking.

The alternatively spliced RECK transcript variant 3 is a predictor of poor survival for melanoma patients being upregulated in aggressive cell lines and modulating MMP gene expression in vitro.

The reversion-inducing cysteine-rich protein with kazal motifs (RECK) gene was described as a tumor suppressor gene two decades ago. Recently, novel alternatively spliced products of this gene have been identified. Of these, the transcript variant 3 (RECKVar3) was shown to display tumor-facilitating effects in astrocytoma cells in vitro, with a higher RECKVar3/canonical RECK expression ratio being correlated with lower survival rates of patients.

Increased Mmp/Reck Expression Ratio Is Associated with Increased Recognition Memory Performance in a Parkinson's Disease Animal Model.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide. Among its non-motor symptoms, sleep disorders are extremely common, being linked to cognitive and memory disruption. The microenvironment, particularly the extracellular matrix (ECM), is deeply involved in memory consolidation as well as in neuropathological processes, such as inflammation, damage to the blood-brain barrier and neuronal death.

CHD7 promotes glioblastoma cell motility and invasiveness through transcriptional modulation of an invasion signature.

Chromatin remodeler proteins exert an important function in promoting dynamic modifications in the chromatin architecture, performing a central role in regulating gene transcription. Deregulation of these molecular machines may lead to striking perturbations in normal cell function. The CHD7 gene is a member of the chromodomain helicase DNA-binding family and, when mutated, has been shown to be the cause of the CHARGE syndrome, a severe developmental human disorder.