卷 25, 编号 7 (2024)

Life Sciences

A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Bioactive Peptides

Singh K., Gupta J., Kumar S., Soni U.

摘要

:Neurodegenerative disorders, which include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), represent a significant and growing global health challenge. Current therapies predominantly focus on symptom management rather than altering disease progression. In this review, we discuss the major therapeutic strategies in practice for these disorders, highlighting their limitations. For AD, the mainstay treatments are cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. For PD, dopamine replacement therapies, including levodopa, are commonly used. HD is managed primarily with symptomatic treatments, and reusable extends survival in ALS. However, none of these therapies halts or substantially slows the neurodegenerative process. In contrast, this review highlights emerging research into bioactive peptides as potential therapeutic agents. These naturally occurring or synthetically designed molecules can interact with specific cellular targets, potentially modulating disease processes. Preclinical studies suggest that bioactive peptides may mitigate oxidative stress, inflammation, and protein misfolding, which are common pathological features in neurodegenerative diseases. Clinical trials using bioactive peptides for neurodegeneration are limited but show promising initial results. For instance, hemiacetal, a γ-secretase inhibitor peptide, has shown potential in AD by reducing amyloid-beta production, though its development was discontinued due to side effects. Despite these advancements, many challenges remain, including identifying optimal peptides, confirming their mechanisms of action, and overcoming obstacles related to their delivery to the brain. Future research should prioritize the discovery and development of novel bioactive peptides and improve our understanding of their pharmacokinetics and pharmacodynamics. Ultimately, this approach may lead to more effective therapies for neurodegenerative disorders, moving beyond symptom management to potentially modify the course of these devastating diseases.

Current Protein & Peptide Science. 2024;25(7):507-526
pages 507-526 views

Research Progress on Extracellular Matrix Involved in the Development of Preeclampsia

Wang X., Zhang Q., Ren Y., Liu C., Gao H.

摘要

:Preeclampsia (PE) is a serious pregnancy complication, and its primary clinical manifestations are gestational hypertension and proteinuria. Trophoblasts are responsible for the basic functions of the placenta during placental development; recent studies have revealed that placental "shallow implantation" caused by the decreased invasiveness of placental trophoblasts plays a crucial role in PE pathogenesis. The interaction between the cells and the extracellular matrix (ECM) plays a crucial role in trophoblast proliferation, differentiation, and invasion. Abnormal ECM function can result in insufficient migration and invasion of placental trophoblasts, thus participating in PE. This article summarizes the recent studies on the involvement of ECM components, including small leucine-rich proteoglycans, syndecans, glypicans, laminins, fibronectin, collagen, and hyaluronic acid, in the development of PE. ECM plays various roles in PE development, most notably by controlling the activities of trophoblasts. The ECM is structurally stable and can serve as a biological diagnostic marker and therapeutic target for PE.

Current Protein & Peptide Science. 2024;25(7):527-538
pages 527-538 views

A Review on Anaplastic Lymphoma Kinase (ALK) Rearrangements and Mutations: Implications for Gastric Carcinogenesis and Target Therapy

Mesquita F., Lima L., da Silva E., Souza P., de Moraes M., Burbano R., Montenegro R.

摘要

Gastric adenocarcinoma is a complex disease with diverse genetic modifications, including Anaplastic Lymphoma Kinase (ALK) gene changes. The ALK gene is located on chromosome 2p23 and encodes a receptor tyrosine kinase that plays a crucial role in embryonic development and cellular differentiation. ALK alterations can result from gene fusion, mutation, amplification, or overexpression in gastric adenocarcinoma. Fusion occurs when the ALK gene fuses with another gene, resulting in a chimeric protein with constitutive kinase activity and promoting oncogenesis. ALK mutations are less common but can also result in the activation of ALK signaling pathways. Targeted therapies for ALK variations in gastric adenocarcinoma have been developed, including ALK inhibitors that have shown promising results in pre-clinical studies. Future studies are needed to elucidate the ALK role in gastric cancer and to identify predictive biomarkers to improve patient selection for targeted therapy. Overall, ALK alterations are a relevant biomarker for gastric adenocarcinoma treatment and targeted therapies for ALK may improve patients' overall survival.

Current Protein & Peptide Science. 2024;25(7):539-552
pages 539-552 views

Phase Separation of Chromatin Structure-related Biomolecules: A Driving Force for Epigenetic Regulations

Wang J., Chen Y., Xiao Z., Liu X., Liu C., Huang K., Chen H.

摘要

Intracellularly, membrane-less organelles are formed by spontaneous fusion and fission of macro-molecules in a process called phase separation, which plays an essential role in cellular activities. In certain disease states, such as cancers and neurodegenerative diseases, aberrant phase separations take place and participate in disease progression. Chromatin structure-related proteins, based on their characteristics and upon external stimuli, phase separate to exert functions like genome assembly, transcription regulation, and signal transduction. Moreover, many chromatin structure-related proteins, such as histones, histone-modifying enzymes, DNA-modifying enzymes, and DNA methylation binding proteins, are involved in epigenetic regulations through phase separation. This review introduces phase separation and how phase separation affects epigenetics with a focus on chromatin structure-related molecules.

Current Protein & Peptide Science. 2024;25(7):553-566
pages 553-566 views

Targeted Delivery of Diphtheria Toxin into VEGFR1/VEGFR2 Overexpressing Cells Induces Anti-angiogenesis Activity

Kazemi-Lomedasht F., Taghizadeh-Hesary F., Faal Z., Behdani M.

摘要

Background::Vascular Endothelial Growth Factor Receptors (VEGFR1 and VEGFR2) are tyrosine kinase receptors expressed on endothelial cells and tumor vessels and play an important role in angiogenesis. In this study, three repeats of VEGFR1 and VEGFR2 binding peptide (VGB3) were genetically fused to the truncated diphtheria toxin (TDT), and its in vitro activity was evaluated.

Methods::The recombinant construct (TDT-triVGB3) was expressed in bacteria cells and purified with nickel affinity chromatography. The binding capacity and affinity of TDT-triVGB3 were evaluated using the enzyme-linked immunosorbent assay. The inhibitory activity of TDT-triVGB3 on viability, migration, and tube formation of human endothelial cells was evaluated using MTT, migration, and tube formation assays.

Results::TDT-triVGB3 selectively detected VEGFR1 and VEGFR2 with high affinity in an enzyme- linked immunosorbent assay and significantly inhibited viability, migration, and tube formation of human endothelial cells.

Conclusion::The developed TDT-triVGB3 is potentially a novel agent for targeting VEGFR1/ VEGFR2 over-expressing cancer cells.

Current Protein & Peptide Science. 2024;25(7):567-576
pages 567-576 views

Knockdown of Ubiquitin-Conjugating Enzyme E2 T Abolishes the Progression of Head and Neck Squamous Cell Carcinoma by Inhibiting NF-Κb Signaling and inducing Ferroptosis

Cai F., Xu H., Song S., Wang G., Zhang Y., Qian J., Xu L.

摘要

Background:Ubiquitin-conjugating enzyme 2T (UBE2T) has been reported to be associated with uncontrolled cell growth and tumorigenesis in multiple cancer types. However, the understanding of its regulatory role in the carcinogenesis of Head And Neck Squamous Cell Carcinoma (HNSC) is limited.

Methods:UBE2T expression in HNSC patient samples and the correlation between its expression and patients’ survival rates were evaluated using The Cancer Genome Atlas (TCGA) database. Cell survival and proliferation were investigated in UM-SCC1 and UM-SCC15 cells infected with control and shUBE2T lentivirus. The xenograft mouse model was established using UM-SCC15 cells to examine HNSC tumorigenesis with or without UBE2T. Western blot, qRT-PCR, and ferroptosis assays were carried out to disclose the interaction between UBE2T and NF-κB signaling and ferroptosis.

Results:The increased expression of UBE2T was noted in tumor tissues of patients with HNSC, correlating with a significantly reduced overall survival time in this patient cohort. Knockdown of UBE2T inhibited HNSC tumorigenesis and tumor growth. Mechanistically, inhibition of UBE2T suppressed NF-κB signaling and induced ferroptosis in HNSC.

Conclusion:Our study underscores the multifaceted role of UBE2T in HNSC, illuminating its potential as a biomarker and therapeutic target.

Current Protein & Peptide Science. 2024;25(7):577-585
pages 577-585 views