98%
921
2 minutes
20
Proper folding is essential for the biological functions of all proteins. The folding process is intrinsically error-prone, and the misfolding of a polypeptide chain can cause the formation of toxic aggregates related to pathological outcomes such as neurodegenerative disease and diabetes. Chaperones and some enzymes are involved in the cellular proteostasis systems that assist polypeptide folding to diminish the risk of aggregation. Elucidating the molecular mechanisms of chaperones and related enzymes is important for understanding proteostasis systems and protein misfolding- and aggregation-related pathophysiology. Furthermore, mechanistic studies of chaperones and related enzymes provide important clues to designing chemical mimics, or chemical chaperones, that are potentially useful for recovering proteostasis activities as therapeutic approaches for treating and preventing protein misfolding-related diseases. In this Perspective, we provide a comprehensive overview of the latest understanding of the folding-promotion mechanisms by chaperones and oxidoreductases and recent progress in the development of chemical mimics that possess activities comparable to enzymes, followed by a discussion of future directions.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10866363 | PMC |
http://dx.doi.org/10.1039/d3sc05781j | DOI Listing |
Appl Environ Microbiol
September 2025
Bacterial Cell Biology, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
The gram-positive bacterium is widely used for enzyme production, especially due to its superior protein secretion capacity. In this study, we have investigated how efficient transcriptome analysis can identify general and protein-specific secretion stress. For this, we constructed strains overproducing different commercially relevant proteins, including a GFP-specific camelid nanobody (GFPnb), the xylanase XynA and the protein glutaminase PrgA, and expressed these proteins either from the strong constitutive P promoter or from the xylose-inducible P promoter.
View Article and Find Full Text PDFInflamm Res
September 2025
Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
Background: Sepsis-Associated Encephalopathy (SAE) is a severe neurological complication of sepsis, where neuroinflammation plays a critical pathogenic role, leading to cognitive dysfunction. The Sigma-1 receptor (Sigma-1R), a chaperone protein, is implicated in neuroprotection, including the crucial modulation of neuroinflammation and endoplasmic reticulum stress (ERS). This study aimed to investigate the therapeutic potential of the Sigma-1R agonist, PRE-084, in specifically targeting SAE-associated neuroinflammation and its downstream neuropathology.
View Article and Find Full Text PDFCell Death Differ
September 2025
Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan.
Nucleotide metabolism is essential for fundamental cellular functions such as growth, repair and proliferation. Emerging evidence suggests that metabolic pathways also influence programmed cell death (PCD), though the underlying mechanisms remain poorly understood. One model organism that has provided key insights into the regulation of PCD is Caenorhabditis elegans (C.
View Article and Find Full Text PDFAutophagy
September 2025
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Chaperone-mediated autophagy (CMA), a lysosome-dependent protein degradation pathway, plays a pivotal yet poorly understood role in cellular senescence-related degenerative diseases. Our study sheds light on a novel mechanism whereby UCHL1 plays a crucial role in mitigating nucleus pulposus cell (NPC) senescence and intervertebral disc degeneration (IVDD) by activating CMA to counteract autophagy-dependent ferroptosis. Through sequencing analysis of human samples, we identified UCHL1 as a potential factor influencing disc degeneration.
View Article and Find Full Text PDFFront Immunol
September 2025
College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China.
Background: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with pro-tumor inflammation playing a critical role in its initiation and progression. Chronic inflammation acts as a major driving force and a distinct mechanism underlying tumorigenesis. Although previous studies have demonstrated the importance of the VEGF/p38MAPK and p38MAPK/HSP27 signaling pathways in CRC-associated inflammation, a comprehensive understanding of the entire pro-tumor inflammatory mechanism remains incomplete.
View Article and Find Full Text PDF