Therapeutic proteins have unique advantages over small-molecule drugs in the treatment of various diseases, such as higher target specificity, stronger pharmacological efficacy and relatively low side effects. These advantages make them increasingly valued in drug development and clinical practice. However, although highly valued, the intrinsic limitations in their physical, chemical and pharmacological properties often restrict their wider applications. As one of the most important post-translational modifications, glycosylation has been shown to exert positive effects on many properties of proteins, including molecular stability, and pharmacodynamic and pharmacokinetic characteristics. Glycoengineering, which involves changing the glycosylation patterns of proteins, is therefore expected to be an effective means of overcoming the problems of therapeutic proteins. In this review, we summarize recent efforts and advances in the glycoengineering of erythropoietin and IgG monoclonal antibodies, with the goals of illustrating the importance of this strategy in improving the performance of therapeutic proteins and providing a brief overview of how glycoengineering is applied to protein-based drugs.
Introduction: Methyltransferase-like protein 3 (METTL3), in complex with METTL14, is the key 'writer' protein for RNA mA methylation, accounting for almost all mRNA mA modifications. Recent studies reveal that METTL3 is implicated in the development and progression of various types of cancers. Targeting METTL3 with small molecule inhibitors represents a promising therapeutic strategy for cancer.
Defective clearance and accumulation of α-synuclein (α-Syn) is the key pathogenic factor in Parkinson's disease (PD). Recent studies emphasize the importance of E3 ligases in regulating the degradation of α-Syn. However, the molecular mechanisms by which deubiquitinases regulate α-Syn degradation are scarcely studied.
There is an urgent necessity to devise efficient tactics to tackle the inevitable development of resistance to osimertinib, which is a third-generation epidermal growth factor receptor (EGFR) inhibitor used in treating EGFR-mutant nonsmall cell lung cancer (NSCLC). This study demonstrates that combining itraconazole with osimertinib synergistically reduces the proliferation and migration, enhances the apoptosis of osimertinib-resistant cells, and effectively inhibits the growth of osimertinib-resistant tumors. Mechanistically, itraconazole combined with osimertinib promotes the proteasomal degradation of sonic hedgehog (SHH), resulting in inactivation of the SHH/Dual-specificity phosphatase 13B (DUSP13B)/p-STAT3 and Hedgehog pathways, suppressing Myc proto-oncogene protein (c-Myc).
Low-frequency non-syndromic hearing loss (LFNSHL) is a rare auditory disorder affecting frequencies ≤ 2000 Hz. To elucidate its genetic basis, we conducted whole-exome sequencing on nine Chinese families (31 affected individuals) with LFNSHL. Four heterozygous pathogenic variants, including two novel variants, were identified in common LFNSHL-related genes (WFS1, DIAPH1) and less common genes (TNC, EYA4), achieving a 44% genetic diagnosis rate.
Background: Chemotherapy-induced mucositis (CIM) significantly impacts quality of life and reduces survival in patients treated with specific chemotherapeutic agents. However, effective clinical treatments for CIM remain limited. Intravenous immunoglobulin (IVIg), a therapeutic derived from pooled human plasma, is widely used to treat inflammatory diseases.
