Current protein & peptide science最新文献

Introduction: Neuroinflammation, axonal damage, and alterations in extracellular matrix (ECM) protein expression are hallmarks of neurodegenerative diseases. Therapies that enhance recovery from brain injury are of significant clinical value. Therefore, this study investigated the antiinflammatory properties of protocatechuic acid (PCA).

Methods: Neuroglial cocultures were prepared from P0-P1 rats. Demyelination was induced using LPC (0.003%). The effects of PCA (10 and 25 μg) on neurite outgrowth were assessed using morphometry software. Expression of COX-2, NF-κβ, PKC-α, and p38/MAPK was examined through immunostaining, SDS-PAGE, and Western blotting. Expression intensities were quantified using ImageJ software. Sustained repetitive neuronal firing was evaluated using the patch-clamp technique.

Results: PCA increased neurite outgrowth in LPC-treated cultures after 72 hours in vitro. LPCinduced upregulation of ECM proteins TN-C, LN, and CSPGs was significantly reduced by PCA treatment compared with LPC controls. Similarly, PCA decreased the expression intensities of the pro-inflammatory markers NF-κβ and COX-2 relative to LPC controls. Furthermore, PCA reversed the sustained neuronal firing pattern observed in untreated LPC-exposed neurons.

Discussion: Purified bioactive compounds commonly present in everyday foods show therapeutic potential for Parkinson's and Alzheimer's diseases due to their lower toxicity compared with conventional drugs. Artificial intelligence tools, such as AlphaFold and RoseTTAFold, further support drug development by predicting PCA binding modes with PKCα and P38/MAPK, thereby contributing to the design of personalized therapeutics and advancing neuroscience research.

Conclusion: PCA alleviated neuroinflammation by reducing phosphorylation of PKCα and p38/MAPK.

Introduction: The pathogenesis of age-related hearing loss (ARHL), especially the role of long non-coding RNAs (lncRNAs) and their encoded peptides, remains incompletely understood. This study aimed to characterize expression changes in lncRNAs and peptides in the cochleae of ARHL mice and explore the potential functions of lncRNA-encoded peptides via multi- -omics analysis.

Methods: C57BL/6J mice were used to establish the ARHL model. The molecular expression profiles of cochlear tissues from normal and ARHL mice were synthesized by lncRNA sequencing, peptidomics, and bioinformatics.

Results: Compared with the control group, a total of 789 differentially expressed lncRNAs and 466 differentially expressed peptides were identified in the ARHL group. Functional enrichment analysis revealed their association with key pathways, including ion transport, calcium signaling, the TCA cycle, and cytoskeleton regulation, indicating broad molecular dysregulation in the aging cochlea. Notably, 64 differentially expressed lncRNAs showed high translational potential, yielding 107 novel lncRNA-encoded peptides. These were mainly short peptides, some with stabilizing hydrophobic properties suited for membrane interactions, and enriched in domains like Pkinase and C2, suggesting involvement in signal transduction.

Discussion: These results emphasized that lncRNA-encoded peptides were novel regulators of ARHL, potentially regulating calcium homeostasis and mitochondrial function. The overlap of pathways such as the cytoskeleton and fatty acid metabolism indicated that the lncRNA-peptide axis drove auditory decline, providing institutional insights into the epigenetic basis of ARHL.

Conclusion: Our findings suggest that lncRNA-encoded peptides are a novel class of regulatory molecules involved in the complex pathogenesis of ARHL, highlighting them as promising targets for future therapeutic strategies.

Apoptosis, drug resistance, and cellular metabolism are all crucially regulated by mitochondria, especially through ion channels and translocases embedded in their membranes. The outer mitochondrial membrane (OMM) contains the voltage dependent anion channel (VDAC), which acts with proteins such as hexokinase II and BAX to regulate apoptosis and metabolic reprogramming in cancer while facilitating the flow of important metabolites and ions. Anti apoptotic proteins like Bcl2 and Mcl1 closely regulate the mitochondrial apoptosis induced channel (MAC), which is created by pro-apoptotic Bcl2 family members BAX and BAK and controls cytochrome c release when overexpressed, leading to drug resistance. Furthermore, the translocase of the outer membrane (TOM) complex, which regulates mitochondrial protein import, is frequently dysregulated in cancers. Numerous ion channels, such as potassium channels, the mitochondrial calcium uniporter (MCU), and the mitochondrial permeability transition pore (m-PTP), are found within the inner mitochondrial membrane (IMM) and regulate important functions like ATP synthesis, the control of reactive oxygen species (ROS), and apoptotic signaling. Cancer cells can avoid apoptosis, adapt to environmental stress, and become resistant to treatments like doxorubicin and cisplatin when these channels are dysregulated. Metabolic flexibility and antioxidant defense are improved by overexpressing or functionally modifying IMM potassium channels and calcium transporters. Additionally, drug resistance is facilitated by increased mitophagy and anti-apoptotic proteins that inhibit m-PTP opening. This review discusses the functions of mitochondrial ion channels.

Sarcopenia and osteoporosis are conditions characterized by the synergistic effects of sarcopenia and osteoporosis, leading to the loss of muscle mass, muscle strength, bone density, and bone quality. This condition is marked by a high disability rate, limited diagnostic and therapeutic options, and significant clinical harm. The pathogenesis of sarcopenia and osteoporosis involves diminished differentiation of osteoblasts and myoblasts, as well as enhanced proliferation of osteoclasts. Signaling pathways such as Wnt/β-catenin, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), and nuclear factor-κB (NF-κB) play crucial roles in promoting the differentiation of osteoblasts and myoblasts while inhibiting osteoclast differentiation, thereby contributing to the treatment of sarcopenia and osteoporosis. Traditional Chinese medicine (TCM) has demonstrated significant efficacy in addressing "muscle atrophy" and "bone depletion." Both single herbs and compound formulas can achieve therapeutic effects on sarcopenia and osteoporosis by modulating the expression of these signaling pathways. By summarizing the current research on these signaling pathways and TCM interventions, we aim to provide new insights for the clinical prevention and treatment of sarcopenia and osteoporosis using TCM and offer a foundation for further in-depth studies.

Plant-based proteins are receiving increasing attention as sustainable and healthconscious alternatives to animal-derived proteins, addressing both environmental concerns and growing consumer demand. This review explores key plant protein sources-including cereals, legumes, pseudocereals, nuts, and seeds-which often provide protein content comparable to or greater than that of milk and meat. The review highlights various production techniques such as extrusion processing for meat-like textures and traditional fermentation methods. Plant molecular farming, using microalgae, plant cells, and whole plants, has emerged as a promising strategy for recombinant protein production. Extraction methods-mechanical, solvent-based, and enzyme-assisted-are also discussed, along with recent innovations like ultrasound- and microwave-assisted extraction. By examining the nutritional quality, processing methods, and potential applications of plant proteins, this review underscores their significance in achieving global food security and promoting sustainable dietary practices.

Sciatic nerve injury represents a prevalent and incapacitating condition characterized by denervation, muscular atrophy, and compromised functionality. The Protein Kinase B (PKB)/ Akt signaling cascade serves as a vital modulator of skeletal muscle hypertrophy, metabolic processes, and regenerative capabilities. Subsequent to sciatic nerve injury, the PI3K/Akt signaling pathway exhibits dysregulation, exacerbating muscle atrophy and hindering recovery processes due to feedback inhibition of PKB/Akt phosphorylation by mTORC1, which consequently increases the expression of E3 ubiquitin ligases and causes muscle atrophy. Additionally, a multitude of other variables, encompassing neurotrophic factors, intracellular calcium ion concentrations, carboxyl-terminal modulator proteins, connexins, and tumor necrosis factor-α, either exert regulatory influences on Akt or are subject to regulation by Akt in a multifaceted manner. Hence, this review discusses the complex role of the PI3K/Akt signaling pathway in skeletal muscle dynamics following sciatic nerve injury, emphasizing its regulatory mechanisms and downstream effectors, and highlights strategies to target this pathway to enhance muscle regeneration and restore functional capabilities.

The chemerin chemokine-like receptor 1 (CHEMR23), a member of the G proteincoupled receptor (GPCR) family, has emerged as a key regulator of immune homeostasis and skeletal remodeling. Notably, CHEMR23 exhibits ligand-specific biased agonism, enabling divergent intracellular signaling pathways depending on the ligand involved. Pro-inflammatory ligands such as chemerin predominantly activate Gi/o protein-dependent cascades, promoting cytokine release, osteoclastogenesis, and tissue degradation. In contrast, the binding of specialized proresolving mediators (SPMs), such as resolvins, preferentially triggers β-arrestin-mediated signaling. This pathway suppresses NF-κB activation, promotes macrophage polarization toward a proresolving phenotype, and facilitates the resolution of inflammation. This signaling bifurcation is particularly relevant in chronic inflammatory diseases characterized by progressive bone loss, including periodontitis. Expression of CHEMR23 is dynamically modulated by inflammatory stimuli, metabolic stress, and genetic polymorphisms, underscoring its potential as a target for resolution- directed therapies. Emerging therapeutic strategies, ranging from lipid-derived SPMs to monoclonal antibodies, are under investigation for their ability to modulate CHEMR23 activity in a ligand- and context-specific manner. This review provides an integrated overview of molecular, cellular, and translational data on CHEMR23, emphasizing its dual functional roles and therapeutic potential in inflammation-associated pathologies.

Hepatocellular carcinoma (HCC) is a highly lethal cancer with a poor prognosis due to difficulties in early diagnosis. In recent years, the roles of FOXM1 and ferroptosis in HCC have attracted attention. FOXM1, a key transcription factor highly expressed in HCC, is closely associated with tumor progression. Ferroptosis, a form of cell death driven by iron metabolism disorders and lipid peroxidation, is closely related to the occurrence and drug resistance of HCC. Studies have shown that FOXM1 significantly influences ferroptosis by regulating genes associated with iron metabolism and antioxidant defenses (such as SLC7A11 and GPX4) and by affecting signaling pathways, like PI3K/Akt/mTOR. Additionally, the interactions of FOXM1 with factors, such as IDO1 and AURKA/NRF2, also modulate the sensitivity of HCC cells to ferroptosis. This review explores the regulatory relationships between FOXM1 and ferroptosis and their potential value in the diagnosis, treatment, and prognosis of HCC, providing a theoretical basis for the development of new therapeutic strategies.

Introduction: Parkinson's disease (PD), a condition that involves neural degeneration, develops due to dopaminergic neuronal death in the substantia nigra pars compacta, resulting in reduced striatal dopamine levels. This shortage causes problems with movement and thinking. The neurodefensive response of GLP-1 is especially important in PD. Assessments have demonstrated the neuroprotective advantages of activating GLP-1 receptors in distinct models of PD, resulting in enhancements in motor as well as non-motor behaviour. These characteristics suggest that GLP-1 signalling could be a promising target for PD treatment. Moreover, plumbagin is the primary active component of Plumbago zeylanica L., a medicinal herb that is clinically used in China. Also, plumbagin is reported to have significant neuroprotective efficacy.

Methods: In this study, male rats received rotenone (1.5 mg/kg; subcutaneously), followed by plumbagin (20 mg/kg; p.o.). The rats' motor abilities were assessed using the actophotometer, beam walk, rotarod, gait analysis, open field, grip strength, as well as bar catalepsy evaluation. In addition, the levels of dopamine, RAGE, and GLP-1 were measured.

Results: Plumbagin improved movement issues caused by rotenone, boosted dopamine and GLP-1 levels, as well as lowered RAGE levels in the brains of rats.

Discussion: The study highlights plumbagin's potential in treating PD by improving motor function, increasing dopamine and GLP-1 levels, and reducing RAGE levels in a rotenone-induced rat model. These findings suggest that plumbagin may offer neuroprotective effects through GLP-1 pathway activation, making it a promising candidate for future PD therapies.

Conclusion: These outcomes imply that agents that activate GLP-1, such as plumbagin, present a promising strategy for creating treatments to safeguard against rotenone-induced motor disorders.

Parkinson's disease (PD) is a neurodegenerative disorder characterized primarily by the progressive loss of dopaminergic neurons in the substantia nigra and the pathological aggregation of α-synuclein. While some genetic and environmental factors contribute to the development of PD, emerging evidence suggests that specific proteins and molecules may have the potential to slow down, reverse, or mitigate the progression of the disease. Recently, the neuroprotective potential of peptide nucleic acid 5 (PNA5) has garnered attention for its ability to restore cognitive functions in PD. PNA5 is an angiotensin (1-7) agonist peptide molecule that targets α-synuclein mRNA to inhibit its translation and aggregation. Key areas explored include the role of PNA5 in reducing toxic α-synuclein oligomers and fibrils, modulating neuroinflammation, preserving mitochondrial function, and harnessing molecular chaperones and angiotensin-MAS receptor signalling pathways for cellular homeostasis. This review emphasizes the significance of PNA5 in addressing the unmet needs of PD treatment, particularly in the areas of memory and cognition. By targeting the molecular basis of cognitive decline, PNA5 represents a transformative candidate for disease-modifying therapy that could revolutionize approaches to treating neurodegenerative disorders. Future studies should concentrate on establishing delivery methods, evaluating long-term efficacy, and addressing safety concerns.