Promising tacrine/huperzine A‐based dimeric acetylcholinesterase inhibitors for neurodegenerative disorders: From relieving symptoms to modifying diseases through multitarget Article Swipe
Shinghung Mak
,
Wenming Li
,
Hongjun Fu
,
Jialie Luo
,
Wei Cui
,
Shengquan Hu
,
Yuan‐Ping Pang
,
Paul R. Carlier
,
Karl Wah Keung Tsim
,
Rongbiao Pi
,
Yifan Han
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1111/jnc.15379
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1111/jnc.15379
Neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, are devastating diseases in the elderly world, which are closely associated with progressive neuronal loss induced by a variety of genetic and/or environmental factors. Unfortunately, currently available treatments for neurodegenerative disorders can only relieve the symptoms but not modify the pathological processes. Over the past decades, our group by collaborating with Profs. Yuan‐Ping Pang and Paul R. Carlier has developed three series of homo/hetero dimeric acetylcholinesterase inhibitors derived from tacrine and/or huperzine A. The representative dimers bis(3)‐Cognitin (B3C), bis(12)‐hupyridone, and tacrine(10)‐hupyridone might possess disease‐modifying effects through the modulation of N ‐methyl‐ d ‐aspartic acid receptors, the activation of myocyte enhancer factor 2D gene transcription, and the promotion of neurotrophic factor secretion. In this review, we summarize that the representative dimers, such as B3C, provide neuroprotection against a variety of neurotoxins via multiple targets, including the inhibitions of N ‐methyl‐ d ‐aspartic acid receptor with pathological‐activated potential, neuronal nitric oxide synthase, and β‐amyloid cascades synergistically. More importantly, B3C might offer disease‐modifying potentials by activating myocyte enhancer factor 2D transcription, inducing neuritogenesis, and promoting the expressions of neurotrophic factors in vitro and in vivo. Taken together, the novel dimers might offer synergistic disease‐modifying effects, proving that dimerization might serve as one of the strategies to develop new generation of therapeutics for neurodegenerative disorders. image
Related Topics
Concepts
Tacrine
Neuroprotection
Huperzine A
Acetylcholinesterase
Neuroscience
Pharmacology
Neurotrophic factors
Brain-derived neurotrophic factor
Chemistry
Medicine
Receptor
Biochemistry
Biology
Enzyme
Metadata
- Type
- review
- Language
- en
- Landing Page
- https://doi.org/10.1111/jnc.15379
- https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jnc.15379
- OA Status
- bronze
- Cited By
- 25
- References
- 136
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3159648298
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3159648298Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1111/jnc.15379Digital Object Identifier
- Title
-
Promising tacrine/huperzine A‐based dimeric acetylcholinesterase inhibitors for neurodegenerative disorders: From relieving symptoms to modifying diseases through multitargetWork title
- Type
-
reviewOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-04-30Full publication date if available
- Authors
-
Shinghung Mak, Wenming Li, Hongjun Fu, Jialie Luo, Wei Cui, Shengquan Hu, Yuan‐Ping Pang, Paul R. Carlier, Karl Wah Keung Tsim, Rongbiao Pi, Yifan HanList of authors in order
- Landing page
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https://doi.org/10.1111/jnc.15379Publisher landing page
- PDF URL
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jnc.15379Direct link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
bronzeOpen access status per OpenAlex
- OA URL
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jnc.15379Direct OA link when available
- Concepts
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Tacrine, Neuroprotection, Huperzine A, Acetylcholinesterase, Neuroscience, Pharmacology, Neurotrophic factors, Brain-derived neurotrophic factor, Chemistry, Medicine, Receptor, Biochemistry, Biology, EnzymeTop concepts (fields/topics) attached by OpenAlex
- Cited by
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25Total citation count in OpenAlex
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2025: 6, 2024: 4, 2023: 7, 2022: 4, 2021: 4Per-year citation counts (last 5 years)
- References (count)
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136Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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