AI Article Synopsis
- Neurodegenerative diseases often show the presence of abnormal protein aggregates, known as inclusion bodies, that were once thought to be the main cause of toxicity.
- However, recent evidence suggests these aggregates may actually serve a protective role within cells rather than directly causing damage.
- The early stages of protein aggregation are likely the most harmful, as they expose certain chemical groups that can interact negatively with other proteins, indicating that similar underlying mechanisms may drive various neurodegenerative diseases and point to potential shared treatment options.
Article Abstract
Neurodegenerative diseases typically involve deposits of inclusion bodies that contain abnormal aggregated proteins. Therefore, it has been suggested that protein aggregation is pathogenic. However, several lines of evidence indicate that inclusion bodies are not the main cause of toxicity, and probably represent a cellular protective response. Aggregation is a complex multi-step process of protein conformational change and accretion. The early species in this process might be most toxic, perhaps through the exposure of buried moieties such as main chain NH and CO groups that could serve as hydrogen bond donors or acceptors in abnormal interactions with other cellular proteins. This model implies that the pathogenesis of diverse neurodegenerative diseases arises by common mechanisms, and might yield common therapeutic targets.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/nrm1742 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Platelet activation and signaling in thrombus formation.
Blood
January 2025
Medical University of Vienna, Vienna, Austria.
In thrombosis and hemostasis, the formation of a platelet-fibrin thrombus or clot is a highly controlled process that varies, depending on the pathological context. Major signaling pathways in platelets are well established. However, studies with genetically modified mice have identified the contribution of hundreds of additional platelet-expressed proteins in arterial thrombus formation and bleeding.
View Article and Find Full Text PDFMechanism of the Discontinuous Structure in Heat-Induced Natural Egg Yolk Mediated by Accumulation of Yolk Sphere Microgels: Morphology, 4D-DIA Proteomics, and Physicochemical Properties.
J Agric Food Chem
January 2025
National Research and Development Center for Egg Processing, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China.
The heat-induced natural egg yolk is a discontinuous object formed by the accumulation of yolk spheres. However, the reason why yolk spheres form individual microgels rather than continuous gels has not been elucidated. This study investigated the different gelation behaviors in the yolk sphere exterior (EYSE) and the yolk sphere interior (EYSI) by using 4D-DIA proteomics, electron microscopy, and multispectral techniques.
View Article and Find Full Text PDFCellular systems that govern protein folding rely on a delicate balance of functional redundancy and diversification to maintain protein homeostasis (proteostasis). Here, we use to demonstrate how both overlapping and divergent activities of two homologous endoplasmic reticulum (ER)-resident HSP70 family chaperones, HSP-3 and HSP-4, orchestrate ER proteostasis and contribute to organismal physiology. We identify tissue-, age-, and stress-specific protein expression patterns and find both redundant and distinct functions for HSP-3 and HSP-4 in ER stress resistance, reproduction, and body size regulation.
View Article and Find Full Text PDFMisfolding and aggregation of proteins into amyloidogenic assemblies are key features of several metabolic and neurodegenerative diseases. Human insulin has long been known to form amyloid fibrils under various conditions, which affects its bioavailability and function. Clinically, insulin aggregation at recurrent injection sites poses a challenge for diabetic patients who rely on insulin therapy.
View Article and Find Full Text PDFEven after folding, proteins transiently sample unfolded or partially unfolded intermediates, and these species are often at risk of irreversible alteration ( via proteolysis, aggregation, or post-translational modification). Kinetic stability, in addition to thermodynamic stability, can directly impact protein lifetime, abundance, and the formation of alternative, sometimes disruptive states. However, we have very few measurements of protein unfolding rates or how mutations alter these rates, largely due to technical challenges associated with their measurement.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!