scholarly journals Cysteine Cathepsins in the secretory vesicle produce active peptides: Cathepsin L generates peptide neurotransmitters and cathepsin B produces beta-amyloid of Alzheimer's disease

2012 ◽  
Vol 1824 (1) ◽  
pp. 89-104 ◽  
Author(s):  
Vivian Hook ◽  
Lydiane Funkelstein ◽  
Jill Wegrzyn ◽  
Steven Bark ◽  
Mark Kindy ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cathepsin B ◽  
Cathepsin L ◽  
Beta Amyloid ◽  
Secretory Vesicle ◽  
Active Peptides ◽  
Cysteine Cathepsins

scholarly journals Identification of Novel Cathepsin B Inhibitors with Implications in Alzheimer’s Disease: Computational Refining and Biochemical Evaluation

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1946
Author(s):  
Nitin Chitranshi ◽  
Ashutosh Kumar ◽  
Samran Sheriff ◽  
Veer Gupta ◽  
Angela Godinez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hydrogen Bond ◽  
Virtual Screening ◽  
Cathepsin B ◽  
Amyloid Β ◽  
Proteolytic Degradation ◽  
Hydrogen Bond Acceptor ◽  
Starting Point ◽  
The Brain

Amyloid precursor protein (APP), upon proteolytic degradation, forms aggregates of amyloid β (Aβ) and plaques in the brain, which are pathological hallmarks of Alzheimer’s disease (AD). Cathepsin B is a cysteine protease enzyme that catalyzes the proteolytic degradation of APP in the brain. Thus, cathepsin B inhibition is a crucial therapeutic aspect for the discovery of new anti-Alzheimer’s drugs. In this study, we have employed mixed-feature ligand-based virtual screening (LBVS) by integrating pharmacophore mapping, docking, and molecular dynamics to detect small, potent molecules that act as cathepsin B inhibitors. The LBVS model was generated by using hydrophobic (HY), hydrogen bond acceptor (HBA), and hydrogen bond donor (HBD) features, using a dataset of 24 known cathepsin B inhibitors of both natural and synthetic origins. A validated eight-feature pharmacophore hypothesis (Hypo III) was utilized to screen the Maybridge chemical database. The docking score, MM-PBSA, and MM-GBSA methodology was applied to prioritize the lead compounds as virtual screening hits. These compounds share a common amide scaffold, and showed important interactions with Gln23, Cys29, His110, His111, Glu122, His199, and Trp221. The identified inhibitors were further evaluated for cathepsin-B-inhibitory activity. Our study suggests that pyridine, acetamide, and benzohydrazide compounds could be used as a starting point for the development of novel therapeutics.

Estrogen, beta-Amyloid Metabolism/Trafficking, and Alzheimer's Disease

2006 ◽  
Vol 1089 (1) ◽  
pp. 324-342 ◽  
Author(s):  
H. XU ◽  
R. WANG ◽  
Y.-W. ZHANG ◽  
X. ZHANG
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Beta Amyloid ◽  
Amyloid Metabolism

Alzheimer's Disease Drugs- In Vitro Comparison of Cholinesterase Inhibition and beta-amyloid Modulation

2017 ◽  
Vol 14 (6) ◽  
Author(s):  
Ondrej Holas ◽  
Jan Korabecny ◽  
Zuzana Gazova ◽  
Katarina Siposova ◽  
Kamil Musilek ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Beta Amyloid ◽  
Cholinesterase Inhibition ◽  
In Vitro Comparison
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