scholarly journals Multitarget drug design strategy in Alzheimer's disease: focus on cholinergic transmission and amyloid-β aggregation

2017 ◽  
Vol 9 (10) ◽  
pp. 953-963 ◽  
Author(s):  
Elena Simoni ◽  
Manuela Bartolini ◽  
Izuddin F Abu ◽  
Alix Blockley ◽  
Cecilia Gotti ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Design ◽  
Amyloid Β ◽  
Design Strategy ◽  
Cholinergic Transmission ◽  
Disease Focus

Minimalistic Design Approach for Multi-Reactivity against Free Radicals and Metal-Free and Metal-Bound Amyloid-β Peptides: Redox-Based Substitutions of Benzene

2019 ◽  
Author(s):  
Mingeun Kim ◽  
Juhye Kang ◽  
Misun Lee ◽  
Jiyeon Han ◽  
Geewoo Nam ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Free Radicals ◽  
Amyloid Β ◽  
Design Strategy ◽  
Design Approach ◽  
Metal Free

We report a minimalistic redox-based design strategy for engineering compact molecules based on the simplest aromatic framework, benzene, with multi-reactivity against free radicals, metal-free amyloid-β, and metal-bound amyloid-β, implicated in the most common form of dementia, Alzheimer’s disease.

Targeted proteomics in Alzheimer’s disease: focus on amyloid-β

2008 ◽  
Vol 5 (2) ◽  
pp. 225-237 ◽  
Author(s):  
Erik Portelius ◽  
Henrik Zetterberg ◽  
Johan Gobom ◽  
Ulf Andreasson ◽  
Kaj Blennow
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Targeted Proteomics ◽  
Disease Focus

Multi-Target-Directed Drug Design Strategy: From a Dual Binding Site Acetylcholinesterase Inhibitor to a Trifunctional Compound against Alzheimer’s Disease

2007 ◽  
Vol 50 (26) ◽  
pp. 6446-6449 ◽  
Author(s):  
Maria Laura Bolognesi ◽  
Andrea Cavalli ◽  
Luca Valgimigli ◽  
Manuela Bartolini ◽  
Michela Rosini ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Design ◽  
Binding Site ◽  
Acetylcholinesterase Inhibitor ◽  
Design Strategy

Neuroinflammation in Alzheimer’s disease: focus on NLRP1 and NLRP3 inflammasomes

2021 ◽  
Vol 22 ◽  
Author(s):  
Eliana Cristina de Brito Toscano ◽  
Natalia Pessoa Rocha ◽  
Beatriz Noele Azevedo Lopes ◽  
Claudia Kimie Suemoto ◽  
Antonio Lucio Teixeira
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Experimental Models ◽  
Tau Pathology ◽  
Relevant Role ◽  
Nlrp3 Inflammasomes ◽  
Amyloid Cascade ◽  
Disease Focus

Background: Alzheimer’s disease (AD) is the main cause of dementia worldwide. The definitive diagnosis of AD is clinicopathological and based on the identification of cerebral deposition of amyloid β (Aβ) plaques and neurofibrillary tangles. However, the link between amyloid cascade and depositions of phosphorylated tau (p-tau) is still missing. In this scenario, inflammasomes might play a relevant role. Experimental models of AD have suggested that Aβ accumulation induces, through microglia, activation of the NLRP3 inflammasome. This activation contributes to the dissemination of Aβ and p-tau, as well as to hyperphosphorylation of tau. Also in experimental models, NLPR1 promoted neuronal pyroptosis. There are neither comprehensive neuropathologic characterization, nor clinicopathologic studies evaluating the NLRP1 and NLRP3 inflammasomes in subjects with AD. Objective: The current mini-review aims to summarize recent and promising findings on the role of NLRP1 and NLRP3 signaling in the pathophysiology of AD. We also sought to highlight the knowledge gap in patients with AD, mainly the lack of clinicopathologic studies on the interaction among inflammasomes, Aβ/tau pathology, and cognitive decline.

Memapsin 2 (β-secretase) as a therapeutic target

2002 ◽  
Vol 30 (4) ◽  
pp. 530-534 ◽  
Author(s):  
L. Hong ◽  
R. T. Turner ◽  
G. Koelsch ◽  
A. K. Ghosh ◽  
J. Tang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Target ◽  
Amyloid Β ◽  
Design Strategy ◽  
Precursor Protein ◽  
Inhibitor Design ◽  
Memapsin 2

As β-secretase, memapsin 2 cleaves amyloid-β precursor protein, which leads ultimately to the onset of Alzheimer's disease. As such, memapsin 2 is an excellent target of inhibitor drugs for the treatment of this disease. Here we describe the tools for memapsin 2 inhibitor design that have been developed and results from the structure-based inhibitor design. Strategy for the design of memapsin 2 inhibitors with pharmaceutical potential is also discussed.

Minimalistic Design Approach for Multi-Reactivity against Free Radicals and Metal-Free and Metal-Bound Amyloid-β Peptides: Redox-Based Substitutions of Benzene

2019 ◽  
Author(s):  
Mingeun Kim ◽  
Juhye Kang ◽  
Misun Lee ◽  
Jiyeon Han ◽  
Geewoo Nam ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Free Radicals ◽  
Amyloid Β ◽  
Design Strategy ◽  
Design Approach ◽  
Metal Free

We report a minimalistic redox-based design strategy for engineering compact molecules based on the simplest aromatic framework, benzene, with multi-reactivity against free radicals, metal-free amyloid-β, and metal-bound amyloid-β, implicated in the most common form of dementia, Alzheimer’s disease.

Amyloid β-peptide and Alzheimer's disease

2014 ◽  
Vol 56 ◽  
pp. 99-110 ◽  
Author(s):  
David Allsop ◽  
Jennifer Mayes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaques ◽  
Strong Support ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Cascade Hypothesis ◽  
Sequence Of Events ◽  
Aβ Amyloid ◽  
Amyloid Cascade

One of the hallmarks of AD (Alzheimer's disease) is the formation of senile plaques in the brain, which contain fibrils composed of Aβ (amyloid β-peptide). According to the ‘amyloid cascade’ hypothesis, the aggregation of Aβ initiates a sequence of events leading to the formation of neurofibrillary tangles, neurodegeneration, and on to the main symptom of dementia. However, emphasis has now shifted away from fibrillar forms of Aβ and towards smaller and more soluble ‘oligomers’ as the main culprit in AD. The present chapter commences with a brief introduction to the disease and its current treatment, and then focuses on the formation of Aβ from the APP (amyloid precursor protein), the genetics of early-onset AD, which has provided strong support for the amyloid cascade hypothesis, and then on the development of new drugs aimed at reducing the load of cerebral Aβ, which is still the main hope for providing a more effective treatment for AD in the future.

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