Protein palmitoylation: biological functions, disease, and therapeutic targets

MedComm, Год журнала: 2025, Номер 6(3)

Опубликована: Фев. 21, 2025

Abstract Protein palmitoylation, a reversible post‐translational lipid modification, is catalyzed by the ZDHHC family of palmitoyltransferases and reversed several acyl protein thioesterases, regulating localization, accumulation, secretion, function. Neurological disorders encompass spectrum diseases that affect both central peripheral nervous system. Recently, accumulating studies have revealed pathological associated with neurological diseases, such as β‐amyloid, α‐synuclein, Huntingtin, could undergo highlighting crucial roles palmitoylation in onset development diseases. However, few preclinical clinical trials focus on interventional strategies target palmitoylation. Here, we comprehensively reviewed emerging evidence role various summarized classification, processes, functions its impact stability, membrane protein–protein interaction, well signal transduction. Furthermore, also discussed potential targeting proteins elucidated their underlying pathogenic mechanisms Overall, an in‐depth understanding significances provide new avenues for investigating therapeutic approaches disorders.

Язык: Английский

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Inhibition of C3a/C3aR by SB290157 Attenuates Neuroinflammation via PKC/P38/NLRP3 Signaling Pathway After Intracerebral Hemorrhage

Neurocritical Care, Год журнала: 2025, Номер unknown

Опубликована: Март 5, 2025

Язык: Английский

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Neuroinflammation—A Crucial Factor in the Pathophysiology of Depression—A Comprehensive Review

Biomolecules, Год журнала: 2025, Номер 15(4), С. 502 - 502

Опубликована: Март 30, 2025

Depression is a multifactorial psychiatric condition with complex pathophysiology, increasingly linked to neuroinflammatory processes. The present review explores the role of neuroinflammation in depression, focusing on glial cell activation, cytokine signaling, blood–brain barrier dysfunction, and disruptions neurotransmitter systems. article highlights how inflammatory mediators influence brain regions implicated mood regulation, such as hippocampus, amygdala, prefrontal cortex. further discusses involvement hypothalamic–pituitary–adrenal (HPA) axis, oxidative stress, kynurenine pathway, providing mechanistic insights into chronic inflammation may underlie emotional cognitive symptoms depression. bidirectional relationship between depressive emphasized, along peripheral immune responses systemic stress. By integrating molecular, cellular, neuroendocrine perspectives, this supports growing field immunopsychiatry lays foundation for novel diagnostic biomarkers anti-inflammatory treatment approaches Further research holds promise developing more effective personalized interventions individuals suffering from

Язык: Английский

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Depletion of HSP60 in Microglia Leads to Synaptic Dysfunction and Depression‐Like Behaviors Through Enhanced Synaptic Pruning in Male Mice

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(4)

Опубликована: Апрель 1, 2025

ABSTRACT Aims Microglia, as resident macrophages in the brain, play an important role depression. Heat shock protein 60 (HSP60), a chaperone protein, plays cell stress. However, of microglial HSP60 depression remains unclear. Methods CX3CR1‐CreER was used to generate microglial‐specific knockout (HSP60 cKO) mice. Behavioral tests, western blotting, Golgi staining, biochemical assays, and proteomics were employed assess depression‐like symptoms, activation, synaptic changes. Results cKO male mice exhibited depressive‐like behaviors, without anxiety‐like behavior, including increased immobility forced swimming tail suspension reduced sucrose preference, elevated corticosterone (CORT) levels, indicating HPA axis activation. Microglial activation confirmed by expression levels CD68 CD86, transcription cybb gene, branch complexity. Enhanced phagocytosis excitatory synapses, dendritic spine density, decreased glutamate observed, with downregulation proteins (AMPAR2, Synapsin‐1, PSD95), dysregulated pruning. Moreover, GO analysis showed 20 significant differentially expressed (DEPs) from are associated presynaptic endosome, which crucial maintaining function. Treatment PLX3397, CSF1R inhibitor, alleviated behaviors restored density Conclusions deletion microglia leads overactivation microglia, impaired function, highlighting importance homeostasis mood regulation potential therapeutic modulation.

Язык: Английский

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Inflammatory pathophysiological mechanisms implicated in postpartum depression

Frontiers in Pharmacology, Год журнала: 2022, Номер 13

Опубликована: Ноя. 3, 2022

Postpartum Depression (PPD) is a serious psychiatric disorder of women within the first year after delivery. It grievously damages women’s physical and mental health. Inflammatory reaction theory well-established in depression, also has been reported associated with PPD. This review summarized inflammatory pathophysiological mechanisms implicated PPD, including decreased T cell activation, increased proinflammatory cytokines secretion, active kynurenine pathway, initiated NLRP3 inflammasome. Clinical preclinical research are both gathered. Potential therapeutical alternatives targeting PPD were introduced. In addition, this briefly discussed differences between depression. The inflammation limited seems just embarking, which indicates direction we can further study. As variety risky factors contribute to collectively, therapy for should be comprehensive, clinical heterogeneity taken into consideration. predictability, early screening interventions needed. aims help readers better understand pathological so as identify biomarkers potential therapeutic targets future.

Язык: Английский

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Potential value of Interleukin-6 as a diagnostic biomarker in human MDD and the antidepressant effect of its receptor antagonist tocilizumab in lipopolysaccharide-challenged rats

International Immunopharmacology, Год журнала: 2023, Номер 124, С. 110903 - 110903

Опубликована: Сен. 18, 2023

Язык: Английский

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Evaluation of the anti-inflammatory material basis of Lagotis brachystachya in HepG2 and THP-1 cells

Journal of Ethnopharmacology, Год журнала: 2023, Номер 318, С. 117055 - 117055

Опубликована: Авг. 18, 2023

Язык: Английский

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Inhibition of colon C5a/C5a receptor signalling pathway confers protection against LPS-induced acute kidney injury via gut microbiota-kidney axis

European Journal of Pharmacology, Год журнала: 2024, Номер 969, С. 176425 - 176425

Опубликована: Фев. 20, 2024

Acute kidney injury (AKI) is a critical condition often associated with systemic inflammation and dysregulated gut microbiota. This study aimed to investigate the effects of C5a receptor antagonist W54011 on lipopolysaccharide (LPS)-induced AKI, focusing colon's C5a/C5a pathway, intestinal barrier integrity, Our findings demonstrate that effectively ameliorated in LPS-induced AKI model by selectively inhibiting signalling pathway. Additionally, blockade resulted inhibition colonic reconstruction mucosal barrier. Furthermore, administration significantly impacted composition stability microbiota, restoring abundance dominant bacteria levels observed normal state flora reducing potentially harmful bacterial groups. In conclusion, alleviates modulating interplay between colon, kidneys. It preserves integrity reinstates thereby mitigating symptoms. These suggest targeting colon microbiota could be promising therapeutic strategy for treatment.

Язык: Английский

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Polygonatum sibiricum Polysaccharides Alleviate Depressive-like Symptoms in Chronic Restraint Stress-Induced Mice via Microglial Regulation in Prefrontal Cortex

Polymers, Год журнала: 2024, Номер 16(16), С. 2358 - 2358

Опубликована: Авг. 20, 2024

Microglia respond to stressors by secreting cytokines or growth factors, playing a crucial role in maintaining brain homeostasis. While the antidepressant-like effects of Polygonatum sibiricum polysaccharides (PSPs) have been observed mice, their potential effectiveness involving microglial regulation remains unknown. This study investigates mechanism PSP regulating phenotype and signaling pathways prefrontal cortex chronic restraint stress (CRS)-induced mice. was extracted, purified, characterized, orally administered CRS High-performance gel permeation chromatography (HPGPC) revealed that has molecular weight 5.6 kDa. Scanning electron microscopy (SEM) atomic force (AFM) showed exhibited layered structure with densely packed, irregular surfaces. treatment significantly increased sucrose preference (low: 71%, p < 0.01; medium: 69%, 0.05; high: 75%, 0.001 vs. CRS: 58%) reduced immobility time 74 s, 68 79 0.05 129 s), indicating alleviation depressive-like behaviors. inhibited activation (PSP, 131/mm2 CRS, 173/mm2, = 0.057), reversing CRS-induced hypertrophy hyper-ramification. Furthermore, inactivated inhibiting NLRP3/ASC/caspase-1/IL-1β pathways, increasing BDNF synthesis activating brain-derived neurotrophic factor (BDNF)-mediated neurogenesis 80/per DG 49/per DG, 0.01). In conclusion, exerts through activity neuroinflammatory it as natural compound for depression treatment.

Язык: Английский

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CY-09 Alleviates the Depression-like Behaviors via Inhibiting NLRP3 Inflammasome-Mediated Neuroinflammation in Lipopolysaccharide-Induced Mice

ACS Chemical Neuroscience, Год журнала: 2022, Номер 13(23), С. 3291 - 3302

Опубликована: Ноя. 18, 2022

Depression is a serious mental illness, mainly characterized as large mood swings and sleep, diet, cognitive function disorders. NLPR3, one of the inflammasomes that can be activated by variety stimuli to promote maturation secretion pro-inflammatory cytokines, has been considered involved in pathophysiology depression. In this study, putative role CY-09, selective direct inhibitor NLRP3, was evaluated lipopolysaccharide (LPS)-induced mice. The results study indicated CY-09 significantly decreased levels NLRP3 hippocampus LPS-induced addition, increased sucrose preference shortened immobility time mice, suggesting antidepressant-like effects inhibiting inflammasome. Biochemical analysis showed LPS NLRP3/ASC/cytokine signaling pathway caused microglial activation, while prevented changes. Moreover, brain-derived neurotrophic factor (BDNF) only microglia but not whole hippocampus. Meanwhile, did neurogenesis conclusion, were mediated alleviating neuroinflammation independent

Язык: Английский

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