scholarly journals Multi-target-directed phenol–triazole ligands as therapeutic agents for Alzheimer's disease

2017 ◽  
Vol 8 (8) ◽  
pp. 5636-5643 ◽  
Author(s):  
Michael R. Jones ◽  
Emilie Mathieu ◽  
Christine Dyrager ◽  
Simon Faissner ◽  
Zavier Vaillancourt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Agents ◽  
Peptide Aggregation ◽  
Primary Neurons ◽  
Aβ Peptide

A series of multi-target-directed ligands are described that bind Cu, act as antioxidants, modulate Aβ peptide aggregation, and abolish Aβ toxicity in primary neurons.

scholarly journals Anti-Aggregation Property of Allicin by In Vitro and Molecular Docking Studies

2019 ◽  
Vol 13 ◽  
pp. 117906951986618 ◽  
Author(s):  
Suresh Kumar ◽  
Shivani Kumar ◽  
Heera Ram
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Molecular Interaction ◽  
Fibril Formation ◽  
Amyloid Peptide ◽  
Peptide Aggregation ◽  
Aβ Peptide ◽  
In Silico Studies

Amyloidogenesis is the process in which amyloid beta (Aβ) peptide aggregation results in plaque formation in central nervous system (CNS) are associated with many neurological diseases such as Alzheimer’s disease. The peptide aggregation initiated from peptide monomers results in formation of dimers, tetramers, fibrils, and protofibrils. The ability of allicin, a lipid-soluble volatile organosulfur biological compound, present in freshly crushed garlic ( Allium sativum L.) to inhibit fibril formation by the Aβ peptide in vitro was investigated in the present study. Inhibition of fibrillogenesis was measured by a Thioflavin T (ThT) fluorescence assay and visualized by transmission electron microscopy (TEM). The molecular interaction between allicin and Aβ peptide was also demonstrated by in silico studies. The results show that allicin strongly inhibited Aβ fibrils by 97% at 300 µM, compared with control (Aβ only) ( P < .001). These results were further validated by visual of fibril formation by transmission microscopy and molecular interaction of amyloid peptide with allicin by molecular docking. Aβ forms favourable hydrophobic interaction with Ile32, Met35, Val36, and Val39, and oxygen of allicin forms hydrogen bond with the amino acid residue Lys28. Allicin anti-amyloidogenic property suggests that this naturally occurring compound may have potential to ameliorate and prevent Alzheimer’s disease.

Recent Progress on the Drug Development for the Treatment of Alzheimer’s Disease Especially on Inhibition of Amyloid-Peptide Aggregation

2020 ◽  
Vol 20 ◽  
Author(s):  
Yuanyuan Liu ◽  
Lin Cong ◽  
Chu Han ◽  
Bo Li ◽  
Rongji Dai
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Development ◽  
Amyloid Peptide ◽  
Research Progress ◽  
Peptide Aggregation ◽  
Aβ Peptide ◽  
Design And Synthesis ◽  
Aggregation Inhibitors ◽  
The Brain

: As the world's population is ageing, Alzheimer’s disease (AD) has become a big concern since patients suffering from AD have become younger and the population of AD patients is increasing worldwide. It has been revealed that the neuropathological hallmarks of AD are typically characterized by the presence of neurotoxic extracellular amyloid plaques in the brain, which are surrounded by tangles of neuronal neuronal fibers. However, the causes of AD have not been completely understood yet. Currently, there is no drug to effectively prevent AD or to completely reserve the symptoms in the patients. This article reviews the pathological features associated with AD, the recent research progress on the drug development to treat AD especially on discovery of natural product derivatives to inhibit Aβ peptide aggregation as well as design and synthesis of Aβ peptide aggregation inhibitors to treat AD.

scholarly journals Mechanism, Diagnosis, Medication, Care Guidance, and Health Promotion in Alzheimer’s Disease

2020 ◽  
Vol 218 ◽  
pp. 03047
Author(s):  
Dong Yue
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Health Care ◽  
Health Promotion ◽  
Daily Activity ◽  
Memory Loss ◽  
Review Article ◽  
Peptide Aggregation ◽  
Aβ Peptide ◽  
Medical Conditions

Alzheimer’s Disease (AD) is one of the most serious and prevalent medical conditions, manifested by memory loss and daily activity dysfunction. Many established hypotheses regarding AD, such as Aβ peptide aggregation and tau tanglements, have provided a fundamental basis. Despite the progress, AD still possesses irreversibility, and the current treatments generated towards AD only aimed to slow down progression. Therefore, further studies on AD mechanism, diagnosis, medication, care guidance, health care and health promotion are constantly conducted for enhancement and advancement. This review article briefly demonstrates long-established facts and sums up the recent discoveries on AD.

scholarly journals A Super-Resolved View of the Alzheimer’s Disease-Related Amyloidogenic Pathway in Hippocampal Neurons

2021 ◽  
pp. 1-20
Author(s):  
Yang Yu ◽  
Yang Gao ◽  
Bengt Winblad ◽  
Lars Tjernberg ◽  
Sophia Schedin Weiss
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hippocampal Neurons ◽  
Three Dimensional ◽  
Amyloid Β ◽  
Stimulated Emission ◽  
Amyloid Β Peptide ◽  
Primary Neurons ◽  
Amyloid Β Protein ◽  
Early Endosomes

Background: Processing of the amyloid-β protein precursor (AβPP) is neurophysiologically important due to the resulting fragments that regulate synapse biology, as well as potentially harmful due to generation of the 42 amino acid long amyloid β-peptide (Aβ 42), which is a key player in Alzheimer’s disease. Objective: Our aim was to clarify the subcellular locations of the amyloidogenic AβPP processing in primary neurons, including the intracellular pools of the immediate substrate, AβPP C-terminal fragment (APP-CTF) and the product (Aβ 42). To overcome the difficulties of resolving these compartments due to their small size, we used super-resolution microscopy. Methods: Mouse primary hippocampal neurons were immunolabelled and imaged by stimulated emission depletion (STED) microscopy, including three-dimensional, three-channel imaging and image analyses. Results: The first (β-secretase) and second (γ-secretase) cleavages of AβPP were localized to functionally and distally distinct compartments. The β-secretase cleavage was observed in early endosomes, where we were able to show that the liberated N- and C-terminal fragments were sorted into distinct vesicles budding from the early endosomes in soma. Lack of colocalization of Aβ 42 and APP-CTF in soma suggested that γ-secretase cleavage occurs in neurites. Indeed, APP-CTF was, in line with Aβ 42 in our previous study, enriched in the presynapse but absent from the postsynapse. In contrast, full-length AβPP was not detected in either the pre- or the postsynaptic side of the synapse. Furthermore, we observed that endogenously produced and endocytosed Aβ 42 were localized in different compartments. Conclusion: These findings provide critical super-resolved insight into amyloidogenic AβPP processing in primary neurons.

scholarly journals Phospholipid dysregulation contributes to ApoE4-associated cognitive deficits in Alzheimer’s disease pathogenesis

2015 ◽  
Vol 112 (38) ◽  
pp. 11965-11970 ◽  
Author(s):  
Li Zhu ◽  
Minghao Zhong ◽  
Gregory A. Elder ◽  
Mary Sano ◽  
David M. Holtzman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Deficits ◽  
Genetic Risk ◽  
Primary Neurons ◽  
Loss Of Function ◽  
Sporadic Alzheimer’S Disease ◽  
Postmortem Human Brain ◽  
Apoe4 Allele ◽  
Synaptojanin 1

The apolipoprotein E4 (ApoE4) allele is the strongest genetic risk factor for developing sporadic Alzheimer’s disease (AD). However, the mechanisms underlying the pathogenic nature of ApoE4 are not well understood. In this study, we have found that ApoE proteins are critical determinants of brain phospholipid homeostasis and that the ApoE4 isoform is dysfunctional in this process. We have found that the levels of phosphoinositol biphosphate (PIP2) are reduced in postmortem human brain tissues of ApoE4 carriers, in the brains of ApoE4 knock-in (KI) mice, and in primary neurons expressing ApoE4 alleles compared with those levels in ApoE3 counterparts. These changes are secondary to increased expression of a PIP2-degrading enzyme, the phosphoinositol phosphatase synaptojanin 1 (synj1), in ApoE4 carriers. Genetic reduction of synj1 in ApoE4 KI mouse models restores PIP2 levels and, more important, rescues AD-related cognitive deficits in these mice. Further studies indicate that ApoE4 behaves similar to ApoE null conditions, which fails to degrade synj1 mRNA efficiently, unlike ApoE3 does. These data suggest a loss of function of ApoE4 genotype. Together, our data uncover a previously unidentified mechanism that links ApoE4-induced phospholipid changes to the pathogenic nature of ApoE4 in AD.

scholarly journals Platinum-based inhibitors of amyloid-  as therapeutic agents for Alzheimer's disease

2008 ◽  
Vol 105 (19) ◽  
pp. 6813-6818 ◽  
Author(s):  
K. J. Barnham ◽  
V. B. Kenche ◽  
G. D. Ciccotosto ◽  
D. P. Smith ◽  
D. J. Tew ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Agents
Sign in / Sign up

Export Citation Format

Share Document