scholarly journals Identification of small molecule drugs that target apolipoprotein E4‐catalyzed amyloid‐β fibrillization: A new therapeutic approach to Alzheimer’s disease

2021 ◽  
Vol 17 (S9) ◽  
Author(s):  
Noah R Johnson ◽  
Athena Ching‐Jung Wang ◽  
Christina M Coughlan ◽  
Stefan H Sillau ◽  
Esteban M Lucero ◽  
...  
2020 ◽  
Vol 16 (S2) ◽  
Author(s):  
Noah R. Johnson ◽  
Athena Ching‐Jung Wang ◽  
Christina M. Coughlan ◽  
Esteban M. Lucero ◽  
Lisa Viltz ◽  
...  

Brain ◽  
2012 ◽  
Vol 135 (7) ◽  
pp. 2155-2168 ◽  
Author(s):  
Robert M. Koffie ◽  
Tadafumi Hashimoto ◽  
Hwan-Ching Tai ◽  
Kevin R. Kay ◽  
Alberto Serrano-Pozo ◽  
...  

2019 ◽  
Vol 01 (01) ◽  
pp. e22-e32
Author(s):  
Sharmin Reza Chowdhury ◽  
Fangzhou Xie ◽  
Jinxin Gu ◽  
Lei Fu

AbstractAlzheimer's disease (AD) is still an incurable neurodegenerative disease that causes dementia. AD changes the brain function that, over time, impairs memory and diminishes judgment and reasoning ability. Pathophysiology of AD is complex. Till now the cause of AD remains unknown, but risk factors include family history and genetic predisposition. The drugs previously approved for AD treatment do not modify the disease process and only provide symptomatic improvement. Over the past few decades, research has led to significant progress in the understanding of the disease, leading to several novel strategies that may modify the disease process. One of the major developments in this direction is the amyloid β (Aβ) aggregation. Small molecules could block the initial stages of Aβ aggregation, which could be the starting point for the design and development of new AD drugs in the near future. In this review we summarize the most promising small-molecule Aβ-aggregation inhibitors including natural compounds, novel small molecules, and also those are in clinical trials. Moreover, we briefly summarized some reported docking studies of small-molecule Aβ aggregation inhibitors. These will give us an idea about the chemical features required to design novel small molecules with anti-Aβ aggregation properties.


2015 ◽  
Vol 6 (3) ◽  
pp. 1879-1886 ◽  
Author(s):  
Michael W. Beck ◽  
Shin Bi Oh ◽  
Richard A. Kerr ◽  
Hyuck Jin Lee ◽  
So Hee Kim ◽  
...  

An in vivo chemical tool designed to target metal−Aβ complexes and modulate their activity was applied to the 5XFAD mouse model of Alzheimer’s disease (AD) demonstrating the involvement of metal−Aβ in AD pathology.


2011 ◽  
Vol 39 (4) ◽  
pp. 924-932 ◽  
Author(s):  
Yadong Huang

ApoE4 (apolipoprotein E4) is the major known genetic risk factor for AD (Alzheimer's disease). In most clinical studies, apoE4 carriers account for 65–80% of all AD cases, highlighting the importance of apoE4 in AD pathogenesis. Emerging data suggest that apoE4, with its multiple cellular origins and multiple structural and biophysical properties, contributes to AD in multiple ways either independently or in combination with other factors, such as Aβ (amyloid β-peptide) and tau. Many apoE mouse models have been established to study the mechanisms underlying the pathogenic actions of apoE4. These include transgenic mice expressing different apoE isoforms in neurons or astrocytes, those expressing neurotoxic apoE4 fragments in neurons and human apoE isoform knock-in mice. Since apoE is expressed in different types of cells, including astrocytes and neurons, and in brains under diverse physiological and/or pathophysiological conditions, these apoE mouse models provide unique tools to study the cellular source-dependent roles of apoE isoforms in neurobiology and in the pathogenesis of AD. They also provide useful tools for discovery and development of drugs targeting apoE4's detrimental effects.


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