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- | Preclinical, Journal: Neuroprotective effects of vitamin D in an Alzheimer's disease rat model: Improvement of mitochondrial dysfunction via calcium/calmodulin-dependent protein kinase kinase 2 activation of Sirtuin1 phosphorylation. (Pubmed Central) - Oct 6, 2023
Vit.D reduced Drp1, induced Mnf1, increased mitochondrial membrane potential, preserved mitochondrial structure, restored normal mitochondrial function, and retained normal eNOS level and SOD activity in AlCl ?+?D-gal rats. In conclusion, our findings proved that Vit.D may ameliorate cognitive deficits in AlCl3?+?D-gal-induced AD by restoring normal mitochondrial function and reducing inflammatory and oxidative stress via CAMKK2-AMPK/SIRT1 pathway upregulation.
- | Journal: Controlled release of Clenbuterol from a hydroxyapatite carrier for the treatment of Alzheimer's Disease. (Pubmed Central) - Oct 5, 2023
In conclusion, our findings proved that Vit.D may ameliorate cognitive deficits in AlCl3?+?D-gal-induced AD by restoring normal mitochondrial function and reducing inflammatory and oxidative stress via CAMKK2-AMPK/SIRT1 pathway upregulation. Our findings suggest that treatment with clenbuterol loaded in this SHAP delivery system could be a promising strategy for treating Alzheimer's disease.
- || Review, Journal: From Mechanisms to Implications: Understanding the Molecular Neurotoxicity of Titanium Dioxide Nanoparticles. (Pubmed Central) - Oct 5, 2023
In addition, TiO2NPs were shown to promote neurotoxic effects of other toxic compounds. Here we show the contribution of a wide spectrum of molecular mechanisms to TiO2NP-induced neurotoxicity; yet, the role of TiO2NP exposure in adverse neurological outcomes in humans has yet to be fully appreciated.
- | Journal: Removal of extracellular human amyloid beta aggregates by extracellular proteases in C. elegans. (Pubmed Central) - Oct 5, 2023
Thus, we provide in-vivo evidence of collagens essential for aggregate formation and metalloprotease participating in extracellular A? aggregate removal.
- | Preclinical, Journal: Detection of Dietary Chalcone and Flavonoid Metabolites in Mice Using UPLC-MS/MS and Their Modulatory Effects on Amyloid ? Aggregation. (Pubmed Central) - Oct 5, 2023
We observed that the conjugated metabolites (sulfate (4) and glucuronide (5)) of 1 prevented the fibrillization and oligomerization of A?42. These findings imply that the conjugated metabolites of 1 can prove beneficial for AD treatment.
- | Journal: The A?42 Peptide and IAPP Physically Interact in a Yeast-Based Assay. (Pubmed Central) - Oct 2, 2023
Our data confirmed a direct physical interaction between IAPP and A?42 aggregates in a living cell. Based on these findings, we hypothesize that this interaction may play a crucial role in seeding A?42 aggregation in T2DM patients, thereby promoting the development of AD.
- | Journal: Imaging Protein Aggregates in Parkinson's Disease Serum Using Aptamer-Assisted Single-Molecule Pull-Down. (Pubmed Central) - Oct 2, 2023
Combining these two metrics, we constructed a new biomarker and achieved an AUC of 0.90. The combination of the aggregate number and morphology provides a new approach to early PD diagnosis.
- | Journal: Self-Assembly Driven Formation of Functional Ultralong "Artificial Fibers" to Mitigate the Neuronal Damage Associated with Alzheimer's Disease. (Pubmed Central) - Sep 28, 2023
Moreover, this injectable, ultralong INHQ functional "artificial fiber" translocates through the blood-brain barrier and successfully attenuates the amyloid-triggered neuronal damage and pyknosis in the cerebral cortex of wild-type mouse. Utilizing various spectroscopic techniques, morphology analysis, and in vitro, in silico, and in vivo studies, these ultralong INHQ fibers are proven to hold great promise for treating neurological disorders at all stages with a potential to replace the existing medications, reduce complications in the brain, and eradicate the amyloid-triggered neurotoxicity implicated in numerous disorders in human through a rare synergistic mechanism.
- | Preclinical, Journal: Morphofunctional Investigation in a Transgenic Mouse Model of Alzheimer's Disease: Non-Reactive Astrocytes Are Involved in A? Load and Reactive Astrocytes in Plaque Build-Up. (Pubmed Central) - Sep 28, 2023
In the late stages of the disease, these patterns were altered in the presence of A?-plaques, surrounded by typically reactive astrocytes and microglia. Morphofunctional characterization of peri-plaque gliosis revealed a direct contribution of astrocytes in plaque buildup that might result in shielding A?-peptide cytotoxicity and, as a side effect, in exacerbating neuroinflammation.
- | Preclinical, Journal: Spectroscopic features of a perylenediimide probe for sensing amyloid fibrils: in vivo imaging of A?-aggregates in a Drosophila model organism. (Pubmed Central) - Sep 27, 2023
The samples from L-Phe-PDI-treated flies apparently displayed reduced fibrillar spots, a possible case of L-Phe-PDI-induced disintegration of fibrillar aggregates at large, an observation substantiated by the improved phenotype activities as compared to the untreated flies. The findings reported both in vitro and in vivo with the L-Phe-PDI material for the first time open up avenues to explore the therapeutic potential of custom-designed PDI derivatives for amyloid fibril sensors and bioimaging.
- | avagacestat (BMS-708163) / BMS
Journal: Bioluminescence Imaging with Functional Amyloid Reservoirs in Alzheimer's Disease Models. (Pubmed Central) - Sep 27, 2023
burdens of the tested AD mice. We believe that our approach can be easily implemented into daily imaging experiments and has tremendous potential to change the daily practice of preclinical AD research.
- | galantamine hydrobromide / Generic mfg.
Preclinical, Journal: Voglibose attenuates cognitive impairment, A? aggregation, oxidative stress, and neuroinflammation in streptozotocin-induced Alzheimer's disease rat model. (Pubmed Central) - Sep 26, 2023
We believe that our approach can be easily implemented into daily imaging experiments and has tremendous potential to change the daily practice of preclinical AD research. In this study, AD was induced in male Wistar rats (n?=?6) by the administration of intracerebroventricular-streptozotocin (ICV-STZ-3
- | Journal: Emodin derivatives as promising multi-aspect intervention agents for amyloid aggregation: molecular docking/dynamics simulation, bioactivities evaluation, and cytoprotection. (Pubmed Central) - Sep 22, 2023
It suggested that a-d could act as the promising multi-targeted directed ligands (MTDLs) for AD. These results may provide meaningful information for the development of the potential MTDLs for AD which are modified from natural-origin scaffolds.
- | Journal: Metal Binding of Alzheimer's Amyloid-? and Its Effect on Peptide Self-Assembly. (Pubmed Central) - Sep 21, 2023
aggregation in vivo, where metal ions are key factors modulating the A? self-assembly and A?-associated neurotoxicity.
- | Journal: Molecular insights into the structure destabilization effects of ECG and EC on the A? protofilament: An all-atom molecular dynamics simulation study. (Pubmed Central) - Sep 20, 2023
Significantly, gallate moiety in ECG had contributed tremendously to the disaggregation. We believed that our findings could be useful for designing prospective drug candidates targeting AD.
- | Journal: CN nanodots inhibits A? peptides aggregation pathogenic path in Alzheimer's disease. (Pubmed Central) - Sep 20, 2023
Finally, molecular dynamics simulations also reveal the inhibitory mechanisms of CN nanodots in A? peptides aggregation and its potential application against AD.
- | Journal: Versatile lipoprotein-inspired nanocomposites rescue Alzheimer's cognitive dysfunction by promoting A? degradation and lessening oxidative stress. (Pubmed Central) - Sep 20, 2023
deposition, decreased the ROS level and improved cognitive functions in AD mice. These findings indicate that multifunctional RLA-rHDL@ANG may serve as a promising and feasible candidate for managing the progression of AD.
- | Targretin oral (bexarotene oral) / ReXceptor
Journal: Nanoscale insights into the local structural rearrangements of amyloid-? induced by bexarotene. (Pubmed Central) - Sep 15, 2023
aggregation by the small molecule drugs. However, our nanoscale findings need to meet in vivo research requiring different analytical approaches.
- | Journal: A novel peptide derived from vascular endothelial growth factor prevents amyloid beta aggregation and toxicity. (Pubmed Central) - Sep 14, 2023
Our findings provide evidence for a neutralizing effect of the BP on A? aggregation process and pathogenic action, highlighting a potential new therapeutic strategy.
- | Journal: Inhibition of Enzymes Involved in Neurodegenerative Disorders and A? Aggregation by Citrus limon Peel Polyphenol Extract. (Pubmed Central) - Sep 13, 2023
These results demonstrate that LPE behaves as a multitargeting agent against key factors of AD and PD by inhibiting to various extents BuChE, MAOs, and SODs and reducing A?-fibril aggregation. Therefore, LPE is a promising candidate for the prevention and management of AD and PD symptoms in combination with pharmacological therapies.
- || Review, Journal: Advances in Alzheimer's Disease-Associated A? Therapy Based on Peptide. (Pubmed Central) - Sep 13, 2023
This review summarizes the design method and characteristics of peptide inhibitors and their effect on the amyloid fibrosis of A?. We further describe some analysis methods for evaluating the inhibitory effect and point out the challenges in these areas, and possible directions for the design of AD drugs based on peptides, which lay the foundation for the development of new effective drugs in the future.
- | Journal: A 4.7-kDa polysaccharide from Panax ginseng suppresses A? pathology via mitophagy activation in cross-species Alzheimer's disease models. (Pubmed Central) - Sep 12, 2023
aggregation was found to be related to its ability to promote neuronal mitophagic activity. This finding offers a robust theoretical foundation for the further development of GP4 as a candidate drugs with the potential to treat AD.
- | Journal: The structurally diverse phytocannabinoids cannabichromene, cannabigerol and cannabinol significantly inhibit amyloid ?-evoked neurotoxicity and changes in cell morphology in PC12 cells. (Pubmed Central) - Sep 12, 2023
These findings highlight the neuroprotective activity of CBC, CBG and CBN as novel pCBs associated with variable effects on A?-evoked neurite damage and inhibition of amyloid ? aggregation.
- | Journal: Anti-Amyloid ? Aggregation Activity and Cell Viability Effect of Betacyanins from Red Pitahaya (Hylocereus polyrhizus) for Alzheimer's Disease. (Pubmed Central) - Sep 12, 2023
aggregation. Further, the betacyanin fraction of 135.78
- || galantamine hydrobromide / Generic mfg., memantine / Generic mfg., rivastigmine / Generic mfg.
Review, Journal: Carbamate as a potential anti-Alzheimer's pharmacophore: A review. (Pubmed Central) - Sep 11, 2023
In this review, we summarize the last 10 years of research conducted on the modification of carbamate with different substituents which primarily target ChE inhibition, reduce oxidative stress, and modulate A? aggregation.
- | Biomarker, Journal: Astrocyte biomarkers GFAP and YKL-40 mediate early Alzheimer's disease progression. (Pubmed Central) - Sep 10, 2023
and insoluble A?. CSF YKL-40 mediated A?-induced tau phosphorylation and tau-induced neuronal injury.
- | Journal: Methylene Blue-Doped Carbonized Polymer Dots: A Potent Photooxygenation Scavenger Targeting Alzheimer's ?-Amyloid. (Pubmed Central) - Sep 9, 2023
This work indicated that potent photooxygenation carbon dots can be obtained by using a photosensitizer as one of the precursors, and the results have provided new insights into the design of potent photooxygenation carbon nanomaterials targeting A? in AD treatment.
- | Preclinical, Journal: Patterning amyloid-? aggregation under the effect of acetylcholinesterase using a biological nanopore - an in vitro study. (Pubmed Central) - Sep 7, 2023
This method will allow future work on testing direct and indirect effects of therapeutic drugs on AChE accelerated A? aggregation as well as disease prognosis.
- | Journal: The Effect of Ultrasonication on the Fibrillar/ Oligomeric Structures of A? at Different Concentrations. (Pubmed Central) - Sep 7, 2023
Cell viability assay indicated that A? oligomers formed at a low concentration (25
- || Preclinical, Review, Journal: Constituent isoflavones of Puerariae radix as a potential neuroprotector in cognitive impairment: Evidence from preclinical studies. (Pubmed Central) - Sep 7, 2023
PR has been used as traditional Chinese herbal medicine for a long time, and its constituent isoflavones exert significant therapeutic effects on CI through various neuroprotective mechanisms. This review will contribute to the future development of isoflavones present in PR as novel drug candidates for the clinical treatment of CI.
- | Journal: Repurposing Antimicrobial Protegrin-1 as a Dual-Function Amyloid Inhibitor via Cross-seeding. (Pubmed Central) - Sep 7, 2023
seeds (K = 1.24-1.90 ?M) through conformationally similar ?-sheet associations. This work introduces a promising strategy to repurpose antimicrobial peptides as amyloid inhibitors, effectively targeting multiple pathological pathways in AD.
- | Preclinical, Journal: Benzo[d]imidazole-pyrrolo[1,2-a]pyrazine Hybrids Ameliorate Amyloid Aggregates in the Brain of Alzheimer Transgenic Mice. (Pubmed Central) - Sep 7, 2023
The ability of YIAD-0205 to ameliorate A? aggregates in the early and mid stages of AD progression supports the notion that YIAD-0205 could be utilized as a reliable scaffold for the development of preventive AD drug candidates.
- | Journal: Multifunctional Supramolecular Vesicles as Zn -Triggered Microglial Modulator Alleviates Alzheimer's Disease. (Pubmed Central) - Sep 7, 2023
With the stereotactic or intranasal administration, RES-loaded vesicles can overcome the blood brain barrier, alleviate neuronal apoptosis, neuroinflammation, and ultimately ameliorate cognitive impairment in two AD mouse models. This work provides a new sight for taking advantage of Zn to treat CNS disorders.
- | Journal: Non-micellar ganglioside GM1 induces an instantaneous conformational change in A? leading to the modulation of the peptide amyloid-fibril pathway. (Pubmed Central) - Sep 7, 2023
Moreover, GM1-modified A? aggregates exhibited prion-like properties in catalyzing the amyloid fibril formation of both major isomers of A?, A?, and A?.
- | Journal: Proteolytically Stable ???-Hybrid Peptides Inhibit the Aggregation and Cytotoxicity of A?. (Pubmed Central) - Sep 1, 2023
showed less tendency for aggregation and also exhibited nontoxicity to the neuronal cells. The results reported here may be useful in designing new therapeutics for Alzheimer's disease.
- | Journal: Design of Self-Assembled Nanoparticles as a Potent Inhibitor and Fluorescent Probe for ?-Amyloid Fibrillization. (Pubmed Central) - Aug 25, 2023
deposition). Therefore, self-assembled nanoparticles hold great potential in AD theranostics.
- | Preclinical, Journal: Mixed Medicinal Mushroom Mycelia Attenuates Alzheimer's Disease Pathologies In Vitro and In Vivo. (Pubmed Central) - Aug 25, 2023
MMMM might mitigate AD-associated memory impairment and cerebral pathologies, including A? plaque accumulation and neuroinflammation, by impeding A?-induced neurotoxicity.
- | Journal: Amphiphilic Molecules Exhibiting Zwitterionic Excited-State Intramolecular Proton Transfer and Near-Infrared Emission for the Detection of Amyloid ? (Pubmed Central) - Aug 24, 2023
aggregates and demonstrated its potential use as an early diagnostic agent for AD. Overall, this study can provide a general molecular design strategy for developing new zwitterionic ESIPT compounds with NIR emission in vivo imaging applications.
- | Journal: Bioactive Isoquinoline Alkaloids with Diverse Skeletons from Fissistigma polyanthum. (Pubmed Central) - Aug 24, 2023
aggregation inhibition, while compounds 13 and 19 simultaneously exhibited discernible AChE and BChE inhibitions with antioxidant activities. The activity results indicate that F. polyanthum alkaloids have a potential of inhibition and prevention of Alzheimer's disease mainly through both ChEs and ?-amyloid pathways in addition to antioxidant activity.
- | Preclinical, Journal: Synergetic effect of ?-asarone and cannabidiol against A? aggregation in vitro and in vivo. (Pubmed Central) - Aug 21, 2023
More importantly, the presence of both compounds synergistically inhibited apoptosis and downregulated relative gene expression in cells, and that it may also slow aging, decrease the rate of paralysis, enhance learning capacity, and boost autophagy activity in C.elegans. Our studies suggest that multiple drugs, like ?-asarone and CBD, may be potentially developed as a medicinal adjunct in the treatment of AD, although further clinical trials are needed to determine the efficacy and safety of this combination treatment in humans.
- | Journal: Multi-target regulatory mechanism of Yang Xin Tang?-?a traditional Chinese medicine against dementia. (Pubmed Central) - Aug 16, 2023
Several constituents of YXT possess multiple regulatory effects on known therapeutic targets of AD that range from ?-amyloid to acetylcholinesterase. The demonstrated neuroprotective and neurogenic actions of YXT lend credence to its use as an alternative medicine for treating AD.
- | Journal: Identification of new pentapeptides as potential inhibitors of amyloid-? aggregation using virtual screening and molecular dynamics simulations. (Pubmed Central) - Aug 14, 2023
monomer to aggregation-prone structures, which, in turn, resulted in a lower aggregation tendency of A? monomer.
- | Preclinical, Journal: Tau and A (Pubmed Central) - Aug 11, 2023
monomer. Tau in these extracts rapidly and persistently disrupted synaptic plasticity and facilitated impairments caused by amyloid
- | Journal: Pterostilbene participates in TLR4- mediated inflammatory response and autophagy-dependent A? endocytosis in Alzheimer's disease. (Pubmed Central) - Aug 10, 2023
Tau in these extracts rapidly and persistently disrupted synaptic plasticity and facilitated impairments caused by amyloid This is the first demonstration that pterostilbene can potentially treat AD by blocking the interaction of TLR4 and MD2, thereby suppressing TLR4-mediated inflammation.
- | Journal: A Hairpin Motif in the Amyloid-? Peptide Is Important for Formation of Disease-Related Oligomers. (Pubmed Central) - Aug 9, 2023
aggregation and suggest that inhibition of A? folding into the hairpin conformation could be a viable strategy for reducing the amount of toxic oligomers.
- | Journal: Sugar distributions on gangliosides guide the formation and stability of amyloid-? oligomers. (Pubmed Central) - Aug 7, 2023
These results demonstrate the selectivity of sugar distributions on the membrane surface toward oligomerization of A? and thus implicate cell-selective enrichment of oligomers.
- | Journal: Characterization of Uranyl (UO) Ion Binding to Amyloid Beta (A?) Peptides: Effects on A? Structure and Aggregation. (Pubmed Central) - Aug 3, 2023
This suggests a possible link between AD and U exposure, which could be further explored by cell, animal, and epidemiological studies. General toxic mechanisms of uranyl ions could be modulation of protein folding, misfolding, and aggregation.
- | Cognex (tacrine) / Shionogi
Journal: Discovery of Multitarget-Directed Ligands from Piperidine Alkaloid Piperine as a Cap Group for the Management of Alzheimer's Disease. (Pubmed Central) - Aug 3, 2023
Further, PD07 increased ACh levels in the brain by inhibiting the AChE activity. The results from in vitro, in silico, and in vivo studies suggested that compound PD07 is a potent multitarget-directed lead from piperine to overcome Alzheimer's disease.
- | Journal: Neuroprotective Effect of NO-Delivery Dinitrosyl Iron Complexes (DNICs) on Amyloid Pathology in the Alzheimer's Disease Cell Model. (Pubmed Central) - Aug 3, 2023
This study found that DNIC-COOH protected neuronal cells from A?-induced cytotoxicity, potentiated neuronal functions, and facilitated A? degradation through the NO-sGC-cGMP-AKT-GSK3?-CREB/MMP-9 pathway.
- | Journal: Amyloid ? Oligomers Induce Galectin-1 O-GlcNAcylation Leading to Microglia Migration. (Pubmed Central) - Aug 2, 2023
Given the importance of microglia migration in the progression of AD, this study reports the relationship between the A? oligomers and Serine 8-O-GlcNAcylation of Galectin-1 to drive microglial migration.