Despite numerous unsuccessful clinical trials for anti-complement drugs to treat age-related macular degeneration (AMD), the complement system has not been fully explored as a target to stop drusen growth in patients with dry AMD. We propose that the resilient autoactivation of C3 by hydrolysis of its internal thioester (tick-over), which cannot be prevented by existing drugs, plays a critical role in the formation of drusenoid deposits underneath the retinal pigment epithelium (RPE). We have combined gene editing tools with stem cell technology to generate cell-based models that allow the role of the tick-over in sub-RPE deposit formation to be studied. The results demonstrate that structurally or genetically driven pathological events affecting the RPE and Bruch's membrane can lead to dysregulation of the tick-over, which is sufficient to stimulate the formation of sub-RPE deposits. This can be prevented with therapies that downregulate C3 expression. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/path.5747 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Preparation of a CNF porous membrane and synthesis of silver nanoparticles (AgNPs).
RSC Adv
January 2025
The Center for Chemical Biology, School of Fundamental Science and Technology, Graduate School of Science and Technology, Keio University 3-14-1 Hiyoshi, Kohoku-ku Yokohama 223-8522 Japan +81-45-566-1580 +81-45-566-1839.
We prepared a cellulose nanofiber (CNF)-based porous membrane with three dimensional cellular structures. CNF was concentrated a surfactant-induced assembly by mixing CNF with a cationic surfactant, domiphen bromide (DB). Furthermore, they were accumulated by centrifugation to obtain a CNF-DB sol.
View Article and Find Full Text PDFInterstitial Doping in Ultrafine Nanocrystals for Efficient and Durable Water Splitting.
Angew Chem Int Ed Engl
January 2025
Nanjing University of Aeronautics and Astronautics, College of Materials Science and Technology, No. 169 Sheng Tai West Road, Jiangning District, Nanjing, Jiangsu, China, 211106, Nanjing, CHINA.
Transition metal-based catalysts with high efficiency and stability for overall water splitting (OWS) offer significant potential for reducing green hydrogen production costs. Utilizing sputtering deposition technology, we propose a deposition-diffusion strategy to fabricate heterojunction coatings composed of ultrafine FeCoNi-C-N transition metal interstitial solid solution (TMISS) nanocrystals and amorphous nitrided carbon (NC) on the pre-deposited NC micro column arrays. The diffusion of C and N atoms results in the formation of uniformly distributed TMISS nanocrystals, with an average diameter of ~1.
View Article and Find Full Text PDFCEST imaging combined with H-MRS reveal the neuroprotective effects of riluzole by improving neurotransmitter imbalances in Alzheimer's disease mice.
Alzheimers Res Ther
January 2025
Radiology Department, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Background: The imbalance of glutamate (Glu) and gamma-aminobutyric acid (GABA) neurotransmitter system plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Riluzole is a Glu modulator originally approved for amyotrophic lateral sclerosis that has shown potential neuroprotective effects in various neurodegenerative disorders. However, whether riluzole can improve Glu and GABA homeostasis in AD brain and its related mechanism of action remain unknown.
View Article and Find Full Text PDFCommon Variants in PLXNA4 and Correlation to Neuroimaging Phenotypes in Healthy, Mild Cognitive Impairment, and Alzheimer's Disease Cohorts.
Mol Neurobiol
January 2025
Department of Neurology, Huai'an First People's Hospital, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, No.1 Huanghe West Road, Huai'an, 223300, Jiangsu, China.
A comprehensive genome-wide association study (GWAS) has validated the identification of the Plexin-A 4 (PLXNA4) gene as a novel susceptibility factor for Alzheimer's disease (AD). Nonetheless, the precise role of PLXNA4 gene polymorphisms in the pathophysiology of AD remains to be established. Consequently, this study is aimed at exploring the relationship between PLXNA4 gene polymorphisms and neuroimaging phenotypes intimately linked to AD.
View Article and Find Full Text PDFMicroenvironment-induced programmable nanotherapeutics restore mitochondrial dysfunction for the amelioration of non-alcoholic fatty liver disease.
Acta Biomater
January 2025
Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, Shandong, 250021, China; Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China. Electronic address:
Nonalcoholic fatty liver disease (NAFLD) is a metabolic liver disorder with severe complications. Mitochondrial dysfunction due to over-opening of the mitochondrial permeability transition pore (mPTP) in liver cells plays a central role in the development and progression of NAFLD. Restoring mitochondrial function is a promising strategy for NAFLD therapy.
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!