Aggregated protein is the common cause of a wide variety of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease, etc. It is proven that protein aggregation like amyloid β (Aβ) is one of the critical factors causing AD and, its diagnosis in the early stages of the disease is important for the treatment or prevention of AD. To have a better understanding of protein aggregation and its pathologies, there is a huge need to design and develop new and more trustworthy probe molecules for amyloid quantification and amyloid imaging. In this study, 17 new biomarker compounds, have been synthesized from benzofuranone derivatives, to detect and identify amyloid in vitro (dye-binding assay) as well as in the cell by staining method. According to the results, some of these synthetic derivatives can be considered suitable identifiers and quantifiers to detect amyloid fibrils . Compared to thioflavin T, 4 probes out of 17 probes have shown good results in selectivity and detectability of Aβ depositions, and their binding properties were also confirmed with analysis. The drug-likeness prediction results for selected compounds by the Swiss ADME server show a satisfactory percentage of blood-brain barrier (BBB) permeability and gastrointestinal (GI) absorption. Among all of them, compound 10 was able to show better binding properties than others, and study showed that this compound was capable of detecting intracellular amyloid.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2023.2184635 | DOI Listing |
Eur J Radiol
January 2025
Department of Radiology, Rouen University Hospital, Rouen, Normandy, France. Electronic address:
Purpose: To evaluate the effectiveness of ultra-fast two-dimensional (2D) T2*-weighted multi-shot echo-planar imaging (MS-EPI) for the detection of cerebral microbleeds (CMB) in cognitive disorders.
Methods: Sixty-eight patients referred for neuroimaging to investigate cognitive disorders underwent 3 T MR imaging, with both 2D T2*-weighted MS-EPI and susceptibility-weighted angiography (SWAN). Microbleeds were separately assessed on 2D T2*-weighted MS-EPI and SWAN by 2 raters.
Chem Commun (Camb)
January 2025
Department of Chemistry, Indian Institute of Technology, Roorkee 247667, India.
KRS-1, a biocompatible nickel(II) complex, is introduced as a potent fluorescent probe for PrP fibrillar aggregates. KRS-1 shows a 15-fold enhancement in PL intensity and detects all stages of PrP aggregation. Fluorescence microscopy confirms its efficacy in identifying PrP fibrillar aggregates in HT-22 cells.
View Article and Find Full Text PDFWorld J Clin Cases
January 2025
Department of Neurology, Guizhou Medical University, Guiyang 550004, Guizhou Province, China.
Dementia is a group of diseases, including Alzheimer's disease (AD), vascular dementia, Lewy body dementia, frontotemporal dementia, Parkinson's disease dementia, metabolic dementia and toxic dementia. The treatment of dementia mainly includes symptomatic treatment by controlling the primary disease and accompanying symptoms, nutritional support therapy for repairing nerve cells, psychological auxiliary treatment, and treatment that improves cognitive function through drugs. Among them, drug therapy to improve cognitive function is important.
View Article and Find Full Text PDFApolipoprotein E4 (APOE4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). Individuals with one copy of APOE4 exhibit greater amyloid-beta (Aβ) deposition compared to noncarriers, an effect that is even more pronounced in APOE4 homozygotes. Interestingly, APOE4 carriers not only show more AD pathology but also experience more rapid cognitive decline, particularly in episodic memory.
View Article and Find Full Text PDFFront Immunol
January 2025
The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United States.
Sepsis is a life-threatening organ dysfunction resulting from a dysregulated host response to infections that is initiated by the body's innate immune system. Nearly a decade ago, we discovered that bacterial lipopolysaccharide (LPS) and serum amyloid A (SAA) upregulated Connexin 43 (Cx43) and Pannexin 1 (Panx1) hemichannels in macrophages. When overexpressed, these hemichannels contribute to sepsis pathogenesis by promoting ATP efflux, which intensifies the double-stranded RNA-activated protein kinase R (PKR)-dependent inflammasome activation, pyroptosis, and the release of pathogenic damage-associated molecular pattern (DAMP) molecules, such as HMGB1.
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