scholarly journals P4-409: Neat, but not beta-amyloid-affinity-depleted, Baxter Immune Globulin® modulates behavior in transgenic mouse expressing Dutch beta-amyloid oligomers

2013 ◽  
Vol 9 ◽  
pp. P885-P885
Author(s):  
Elysse Knight ◽  
Paul Szabo ◽  
Michelle Ehrlich ◽  
Norman Relkin ◽  
Sam Gandy
Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 870 ◽  
Author(s):  
Raluca Stefanescu ◽  
Gabriela Dumitriṭa Stanciu ◽  
Andrei Luca ◽  
Luminita Paduraru ◽  
Bogdan-Ionel Tamba

Alzheimer’s disease is a neurodegenerative disorder for which there is a continuous search of drugs able to reduce or stop the cognitive decline. Beta-amyloid peptides are composed of 40 and 42 amino acids and are considered a major cause of neuronal toxicity. They are prone to aggregation, yielding oligomers and fibrils through the inter-molecular binding between the amino acid sequences (17–42) of multiple amyloid-beta molecules. Additionally, amyloid deposition causes cerebral amyloid angiopathy. The present study aims to identify, in the existing literature, natural plant derived products possessing inhibitory properties against aggregation. The studies searched proved the anti-aggregating effects by the thioflavin T assay and through behavioral, biochemical, and histological analysis carried out upon administration of natural chemical compounds to transgenic mouse models of Alzheimer’s disease. According to our present study results, fifteen secondary metabolites from plants were identified which presented both evidence coming from the thioflavin T assay and transgenic mouse models developing Alzheimer’s disease and six additional metabolites were mentioned due to their inhibitory effects against fibrillogenesis. Among them, epigallocatechin-3-gallate, luteolin, myricetin, and silibinin were proven to lower the aggregation to less than 40%.


2014 ◽  
Vol 9 (1) ◽  
pp. 12
Author(s):  
Virginia Fonte ◽  
Vishantie Dostal ◽  
Christine M Roberts ◽  
Patrick Gonzales ◽  
Pascale N Lacor ◽  
...  

Author(s):  
Ibrahim González-Marrero ◽  
Lydia Giménez-Llort ◽  
Conrad E. Johanson ◽  
Emilia María Carmona-Calero ◽  
Leandro Castañeyra-Ruiz ◽  
...  

2014 ◽  
Vol 107 (7) ◽  
pp. 1601-1608 ◽  
Author(s):  
Jaewook Kim ◽  
Yoosoo Yang ◽  
Seung Soo Song ◽  
Jung-Hyun Na ◽  
Kyoung Joon Oh ◽  
...  

Author(s):  
C Barden ◽  
F Meier-Stephenson ◽  
MD Carter ◽  
S Banfield ◽  
EC Diez ◽  
...  

Background: There are no disease modifying agents for the treatment of Alzheimer’s disease (AD). Pathologically, AD is associated with the misfolding of two peptides: beta-amyloid (plaques) and tau (tangles). Methods: Using large-scale computer simulations, we modelled the misfolding of both beta-amyloid and tau, identifying a common conformational motif (CCM; i.e. an abnormal peptide shape), present in both beta-amyloid and tau, that promotes their misfolding. We screened a library of 11.8 million compounds against this in silico model of protein misfolding, identifying three novel molecular classes of putative therapeutics as anti-protein misfolding agents. We synthesized approximately 400 new chemical entity drug-like molecules in each of these three classes (i.e. 1200 potential drug candidates). These were comprehensively screened in a battery of five in vitro protein oligomerization assays. Selected compounds were next evaluated in the APP/PS1 doubly transgenic mouse model of AD. Results: Two new classes of molecules were identified with the ability to block the oligomerization of both beta-amyloid and tau. These compounds are drug-like with good pharmacokinetic properties and are brain-penetrant. They exhibit excellent efficacy in transgenic mouse models. Conclusion: Computer aided drug design has enabled the discovery of novel drug-like molecules able to inhibit both tau and beta-amyloid misfolding.


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