Polyamines promote the formation of the Aβ peptide amyloid fibers that are a hallmark of Alzheimer's disease. Here we show that polyamines interact with nonaggregated Aβ peptides, thereby reducing the peptide's hydrophobic surface. We characterized the associated conformational change through NMR titrations and molecular dynamics simulations. We found that even low concentrations of spermine, sperimidine, and putrescine fully protected SH-SY5Y (a neuronal cell model) against the most toxic conformational species of Aβ, even at an Aβ oligomer concentration that would otherwise kill half of the cells or even more. These observations lead us to conclude that polyamines interfere with the more toxic prefibrillar conformations and might protect cells by promoting the structural transition of Aβ toward its less toxic fibrillar state that we reported previously. Since polyamines are present in brain fluid at the concentrations where we observed all these effects, their activity needs to be taken into account in understanding the molecular processes related to the development of Alzheimer's disease.
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http://dx.doi.org/10.1021/bm401874j | DOI Listing |
Invest Ophthalmol Vis Sci
January 2025
State Key Laboratory of Ophthalmology, Optometry, and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, China.
Purpose: Changes associated with Alzheimer's disease (AD) may have measurable effects on the retina, which may facilitate early detection due to the eye's accessibility. Retinal pathology and the regulation of serine racemase (SR) were investigated in the retinas of APP(SW)/PS1(∆E9) mice.
Methods: SR in the retinas and the content of D-serine in the aqueous humor were analyzed.
Metab Brain Dis
January 2025
School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700 032, India.
Alzheimer's disease is a complex neurodegenerative disease characterized by progressive decline in cognitive function and behaviour. Ginger is the rhizome of the plant Zingiber officinale Roscoe, has been an important ingredient of many Ayurveda formulations to treat neurological disorders. The present study aims to estimate the variation of 6-gingerol content in nine different ginger samples collected from Manipur, India, investigate the neuroprotective potential of the most potent ginger sample against scopolamine-induced cognitively impaired mice, and validate the therapeutic claim by molecular docking analysis.
View Article and Find Full Text PDFNeuromolecular Med
January 2025
Department of Genetic Engineering & Biotechnology, University of Dhaka, Dhaka, Bangladesh.
Interleukin 6 (IL6) is an inflammatory biomarker linked to central and peripheral nervous system diseases. This study combined bioinformatics and statistical meta-analysis to explore potential associations between IL6 gene variants (rs1800795, rs1800796, and rs1800797) and neurological disorders (NDs) and brain cancer. The meta-analysis was conducted on substantial case-control datasets and revealed a significant correlation between IL6 SNPs (rs1800795 and rs1800796) with overall NDs (p-value < 0.
View Article and Find Full Text PDFJ Neurol
January 2025
Department of Central laboratory, Xuanwu Hospital of Capital Medical University, Beijing, 100053, P.R. China.
Background: Circadian disruptions are increasingly recognized in Alzheimer's disease (AD) patients and may influence disease onset and progression. This study examines how AD pathology affects blood-borne factors that regulate circadian rhythms.
Methods: Eighty-five participants from the Sino Longitudinal Study on Cognitive Decline were enrolled: 35 amyloid-beta negative normal controls (Aβ- NCs), 23 amyloid-beta positive normal controls (Aβ+ NCs), 15 patients with amnestic mild cognitive impairment (aMCI), and 12 with Alzheimer's disease dementia (ADD).
J Exp Med
February 2025
Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.
IKKα, encoded by CHUK, is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKβ. The absence of IKKα causes fetal encasement syndrome in humans, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and causes combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of IKKα in a female patient with hypogammaglobulinemia, recurrent lung infections, and Hay-Wells syndrome-like features.
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