Altered metabolism and DAM-signatures in female brains and microglia with aging

Brain Research, Год журнала: 2024, Номер 1829, С. 148772 - 148772

Опубликована: Янв. 18, 2024

Язык: Английский

---

Decoding Microglial Polarization and Metabolic Reprogramming in Neurodegenerative Diseases: Implications for Disease Progression and Therapy

Aging and Disease, Год журнала: 2025, Номер unknown, С. 0 - 0

Опубликована: Янв. 1, 2025

As the resident macrophages of brain, microglia are crucial immune cells specific to central nervous system (CNS). They constantly surveil their surroundings and trigger immunological reactions, playing a key role in various neurodegenerative diseases (ND). illnesses progress, exhibit multiple phenotypes. Traditionally, have been classified into two main phenotypes upon activation: pro-inflammatory M1 polarization anti-inflammatory M2 polarization. However, this classification is now considered overly simplistic, as it unable fully convey intricacy diversity inflammatory response. Immune regulatory factors, such chemokines secreted by microglia, essential for modulating brain development, maintaining neural milieu, orchestrating responses injury, along with subsequent repair processes. recent years, significance metabolic reprogramming both physiological microglial activity ND has also become increasingly recognized. Upon activation-triggered infection, or ND-microglia typically modify processes transitioning from oxidative phosphorylation (OXPHOS) glycolysis. This shift facilitates rapid energy production but may enhance responses. review seeks summarize function involvement ND.

Язык: Английский

---

The Role of the Urea Cycle in the Alzheimer's Disease Brain

Journal of Neurochemistry, Год журнала: 2025, Номер 169(3)

Опубликована: Фев. 28, 2025

ABSTRACT Alzheimer's Disease (AD) is a neurodegenerative disorder classified as the leading form of dementia in elderly. Classical hallmarks AD pathology believed to cause include Amyloid‐beta (Aβ) plaques well neurofibrillary tau tangles (NTT). However, research into these classical has failed account for causative link or therapeutic success. More recently, metabolic have become popular avenue research. Elevated urea and ammonia detected cases point towards dysfunctional cycle involved AD. This review covers expansive body literature surrounding work researchers deciphering role through study enzymes, metabolites, transporters brain. Urea enzymes interest OTC, NOS isoforms, ARG1, ARG2, MAOB, ODC, which all present promising targets. metabolites indicated varying concentrations across regions brain different cell types (neurons, microglia, astrocytes). Finally, UT‐B clearance modulator presents this protein key target In future, pathways, proteins relating should be further investigated better understand cell‐specific profiles uncover their potential. image

Язык: Английский

---

Microglial Regulation of Neural Networks in Neuropsychiatric Disorders

The Neuroscientist, Год журнала: 2025, Номер unknown

Опубликована: Фев. 11, 2025

Microglia serve as vital innate immune cells in the central nervous system, playing crucial roles generation and development of brain neurons, well mediating a series inflammatory responses. The morphologic transitions microglia are closely linked to their function. With advent single-cell sequencing technology, diversity microglial subtypes is increasingly recognized. intricate interactions between neuronal networks have significant implications for psychiatric disorders neurodegenerative diseases. A deeper investigation neurologic diseases such Alzheimer disease, depression, epilepsy can provide valuable insights understanding pathogenesis exploring novel therapeutic strategies, thereby addressing issues related system disorders.

Язык: Английский

---

Pathogenesis and therapeutic applications of microglia receptors in Alzheimer’s disease

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 14, 2025

Microglia, the resident immune cells of central nervous system, continuously monitor brain’s microenvironment through their array specific receptors. Once brain function is altered, microglia are recruited to sites perform functions, including phagocytosis misfolded proteins, cellular debris, and apoptotic maintain homeostasis. When toxic substances overproduced, over-activated produce large amounts pro-inflammatory cytokines, which induce chronic inflammatory responses lead neurotoxicity. Additionally, can also protect neuronal microglia-neuron crosstalk. Microglia receptors important mediators for receive external stimuli, regulate functional state microglia, transmit signals between cells. In this paper, we first review role microglia-expressed in pathogenesis treatment Alzheimer’s disease; moreover, emphasize complexity targeting therapeutic interventions neurodegenerative disorders inform discovery new biomarkers development innovative therapeutics

Язык: Английский

---

Treadmill Exercise Modulates the Leptin/LepR/GSK-3β Signalling Pathway to Improve Leptin Sensitivity and Alleviate Neuroinflammation in High-Fat Diet-Fed APP/PS1 Mice

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Март 25, 2025

Язык: Английский

---

Decoding microglial immunometabolism: a new frontier in Alzheimer's disease research

Molecular Neurodegeneration, Год журнала: 2025, Номер 20(1)

Опубликована: Март 27, 2025

Abstract Alzheimer’s disease (AD) involves a dynamic interaction between neuroinflammation and metabolic dysregulation, where microglia play central role. These immune cells undergo reprogramming in response to AD-related pathology, with key genes such as TREM2, APOE, HIF-1α orchestrating these processes. Microglial metabolism adapts environmental stimuli, shifting oxidative phosphorylation glycolysis. Hexokinase-2 facilitates glycolytic flux, while AMPK acts an energy sensor, coordinating lipid glucose metabolism. TREM2 APOE regulate microglial homeostasis, influencing Aβ clearance responses. LPL ABCA7, both associated AD risk, modulate processing cholesterol transport, linking neurodegeneration. PPARG further supports by regulating inflammatory Amino acid also contributes function. Indoleamine 2,3-dioxygenase controls the kynurenine pathway, producing neurotoxic metabolites linked pathology. Additionally, glucose-6-phosphate dehydrogenase regulates pentose phosphate maintaining redox balance activation. Dysregulated metabolism, influenced genetic variants APOE4, impair responses exacerbate progression. Recent findings highlight interplay regulators like REV-ERBα, which modulates inflammation, Syk, influences clearance. insights offer promising therapeutic targets, including strategies aimed at modulation, could restore function depending on stage. By integrating metabolic, immune, factors, this review underscores importance of immunometabolism AD. Targeting pathways provide novel for mitigating restoring function, ultimately paving way innovative treatments neurodegenerative diseases.

Язык: Английский

---

Alzheimer’s Disease, Obesity, and Type 2 Diabetes: Focus on Common Neuroglial Dysfunctions (Critical Review and New Data on Human Brain and Models)

Brain Sciences, Год журнала: 2024, Номер 14(11), С. 1101 - 1101

Опубликована: Окт. 30, 2024

Obesity, type 2 diabetes (T2D), and Alzheimer's disease (AD) are pathologies that affect millions of people worldwide. They have no effective therapy difficult to prevent control when they develop. It has been known for many years these diseases pathogenic aspects in common. We highlight this review neuroglial cells (astroglia, oligodendroglia, microglia) play a vital role the origin, clinical-pathological development, course brain neurodegeneration. Moreover, we include new results T2D-AD mouse model (APP+PS1 mice on high-calorie diet) investigating.

Язык: Английский

---

Microglia-Associated Neuroinflammation in Alzheimer’s Disease and Its Therapeutic Potential

Neuroglia, Год журнала: 2024, Номер 5(4), С. 452 - 466

Опубликована: Ноя. 21, 2024

Background: Neuroinflammation has long been implicated in the progression of amyloid beta (Aβ) accumulation and decline cognitive function Alzheimer’s disease (AD). The phenotype balance between A1 (toxic) A2 (safe) microglial phenotypes to toxic illness AD become a hot research topic at present. Currently, many transcription factors, downstream signaling pathways, molecular mechanisms that regulate polarization microglia are being explored. Furthermore, may also exert complex role through transformation Aβ plaques or debris clearance, reflected phagocytosis. One mediators neuroinflammation is activated microglia. Therefore, regulation be key successfully treating AD. Methods: This paper review article. PubMed, Embase, Scopus, meeting abstracts were searched up 2024 for studies Disease. Systematic information retrieval was performed, appropriate isolated based on important available studies. from each articles understood extracted form database. Results: similar neuropathological results several animals cases show possibility implementing microglia-related changes as an earlier diagnostic marker humans. gene sets identified various transcriptomic further foster this avenue by offering potential targets therapeutic development. Substantial evidence, both vitro vivo, suggested loss normal activation contribute neurodegeneration Conclusions: Promoting restoring towards thus represent effective strategy ameliorating progressive neurocognitive impairments. Multiple suggest microglia-associated special stage could protective, and, therefore, intervention should delicate so beneficial response retained.

Язык: Английский

---

Microglia-Associated Neuroinflammation in Alzheimer’s Disease

Опубликована: Июль 22, 2024

Background: Neuroinflammation has long been implicated in the progression of amyloid beta (Aβ) accumulation and decline cognitive function Alzheimer's disease (AD). Currently, many transcription factors, downstream signaling pathways, molecular mechanisms that regulate polarization microglia have explored. Furthermore, may also exert a complex role AD through transformation Aβ plaques or debris clearance, reflected phagocytosis. One mediators neuroinflammation is activated microglia. Therefore, regulation microglial be key to successfully treating AD. Methods: This review article. PubMed, Embase, Scopus, research meeting abstracts were searched up 2024 for studies Disease. Systematic information retrieval was performed appropriate isolated based on important available studies. The from each articles un-derstood extracted form database. Results: similar neuropathological results between several animals cases show possibility implement microglia-related changes as an earlier diagnostic marker humans. gene sets identified various transcriptomic further foster this avenue by offering potential targets therapeutic development. Multiple suggest microglia-associated at special stage could protective, there-fore, intervention should delicate so beneficial response retained. Conclusion: phenotype balance A1 (toxic) A2 (safe) phenotypes toxic illness become hot topic present. Substantial evidence, both vitro vivo, suggested loss normal activation contribute neurodegeneration Promoting restoring mi-croglia towards thus represent effective strategy ame-liorating progressive neurocognitive impairments.

Язык: Английский

---