Novel Anti-Alzheimer's Dimer Bis(7)-Cognitin: Cellular and Molecular Mechanisms of Neuroprotection Through Multiple Targets

Wenming Li, Marvin Mak, Hualiang Jiang, Qinwen Wang, Yuan-Ping Pang, Kaixian Chen, Yifan Han

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is a progressive and degenerative brain disorder that has emerged as one of the major public health problems in adults. Unfortunately, its molecular pathology and therapeutic strategies remain elusive. Because there are multiple factors closely indicated in the pathogenesis of AD, multiple drug therapy will be required to address the varied pathological aspects of this disease. Existing pharmacological approaches with one-molecule-one-target are limited in their ability to modify the pathology of AD. Novel therapeutics strategies comprise multifunctional compounds specifically designed to target concurrently on different sites at multifactorial etiopathogenesis of AD, thereby providing greater therapeutic efficacy. Over the past decade, our group has developed several series of dimeric acetylcholinesterase (AChE) inhibitors derived from tacrine and huperzine A, a unique anti-Alzheimer's drug originally discovered from a traditional Chinese medicinal plant. Bis(7)-Cognitin, one of our novel dimers, through inhibition of AChE, N-methyl-D-aspartate receptor, nitric oxide synthase, and amyloid precursor protein/β-amyloid cascade concurrently, possesses remarkable neuroprotective activities. More importantly, the synergism between these targets might serve as one of the most effective therapeutic strategies to arrest/modify pathological process of AD in addition to improving the cognitive functions for AD.

Original languageEnglish (US)
Pages (from-to)187-201
Number of pages15
JournalNeurotherapeutics
Volume6
Issue number1
DOIs
StatePublished - Jan 2009

Fingerprint

Alzheimer Disease
Tacrine
Aptitude
Molecular Pathology
Amyloid beta-Protein Precursor
Cholinesterase Inhibitors
Brain Diseases
Pathologic Processes
Therapeutics
Acetylcholinesterase
Medicinal Plants
N-Methyl-D-Aspartate Receptors
Amyloid
Nitric Oxide Synthase
Cognition
1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine
Neuroprotection
Public Health
Pharmacology
Pathology

Keywords

  • AChE
  • Bis(7)-Cognitin
  • multiple targets
  • neuroprotection
  • NMDA receptor

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Clinical Neurology
  • Pharmacology

Cite this

Novel Anti-Alzheimer's Dimer Bis(7)-Cognitin : Cellular and Molecular Mechanisms of Neuroprotection Through Multiple Targets. / Li, Wenming; Mak, Marvin; Jiang, Hualiang; Wang, Qinwen; Pang, Yuan-Ping; Chen, Kaixian; Han, Yifan.

In: Neurotherapeutics, Vol. 6, No. 1, 01.2009, p. 187-201.

Research output: Contribution to journalArticle

Li, Wenming ; Mak, Marvin ; Jiang, Hualiang ; Wang, Qinwen ; Pang, Yuan-Ping ; Chen, Kaixian ; Han, Yifan. / Novel Anti-Alzheimer's Dimer Bis(7)-Cognitin : Cellular and Molecular Mechanisms of Neuroprotection Through Multiple Targets. In: Neurotherapeutics. 2009 ; Vol. 6, No. 1. pp. 187-201.
@article{498719da18b74dc5a24fe9801f07f15e,
title = "Novel Anti-Alzheimer's Dimer Bis(7)-Cognitin: Cellular and Molecular Mechanisms of Neuroprotection Through Multiple Targets",
abstract = "Alzheimer's disease (AD) is a progressive and degenerative brain disorder that has emerged as one of the major public health problems in adults. Unfortunately, its molecular pathology and therapeutic strategies remain elusive. Because there are multiple factors closely indicated in the pathogenesis of AD, multiple drug therapy will be required to address the varied pathological aspects of this disease. Existing pharmacological approaches with one-molecule-one-target are limited in their ability to modify the pathology of AD. Novel therapeutics strategies comprise multifunctional compounds specifically designed to target concurrently on different sites at multifactorial etiopathogenesis of AD, thereby providing greater therapeutic efficacy. Over the past decade, our group has developed several series of dimeric acetylcholinesterase (AChE) inhibitors derived from tacrine and huperzine A, a unique anti-Alzheimer's drug originally discovered from a traditional Chinese medicinal plant. Bis(7)-Cognitin, one of our novel dimers, through inhibition of AChE, N-methyl-D-aspartate receptor, nitric oxide synthase, and amyloid precursor protein/β-amyloid cascade concurrently, possesses remarkable neuroprotective activities. More importantly, the synergism between these targets might serve as one of the most effective therapeutic strategies to arrest/modify pathological process of AD in addition to improving the cognitive functions for AD.",
keywords = "AChE, Bis(7)-Cognitin, multiple targets, neuroprotection, NMDA receptor",
author = "Wenming Li and Marvin Mak and Hualiang Jiang and Qinwen Wang and Yuan-Ping Pang and Kaixian Chen and Yifan Han",
year = "2009",
month = "1",
doi = "10.1016/j.nurt.2008.10.040",
language = "English (US)",
volume = "6",
pages = "187--201",
journal = "Neurotherapeutics",
issn = "1933-7213",
publisher = "Springer New York",
number = "1",

}

TY - JOUR

T1 - Novel Anti-Alzheimer's Dimer Bis(7)-Cognitin

T2 - Cellular and Molecular Mechanisms of Neuroprotection Through Multiple Targets

AU - Li, Wenming

AU - Mak, Marvin

AU - Jiang, Hualiang

AU - Wang, Qinwen

AU - Pang, Yuan-Ping

AU - Chen, Kaixian

AU - Han, Yifan

PY - 2009/1

Y1 - 2009/1

N2 - Alzheimer's disease (AD) is a progressive and degenerative brain disorder that has emerged as one of the major public health problems in adults. Unfortunately, its molecular pathology and therapeutic strategies remain elusive. Because there are multiple factors closely indicated in the pathogenesis of AD, multiple drug therapy will be required to address the varied pathological aspects of this disease. Existing pharmacological approaches with one-molecule-one-target are limited in their ability to modify the pathology of AD. Novel therapeutics strategies comprise multifunctional compounds specifically designed to target concurrently on different sites at multifactorial etiopathogenesis of AD, thereby providing greater therapeutic efficacy. Over the past decade, our group has developed several series of dimeric acetylcholinesterase (AChE) inhibitors derived from tacrine and huperzine A, a unique anti-Alzheimer's drug originally discovered from a traditional Chinese medicinal plant. Bis(7)-Cognitin, one of our novel dimers, through inhibition of AChE, N-methyl-D-aspartate receptor, nitric oxide synthase, and amyloid precursor protein/β-amyloid cascade concurrently, possesses remarkable neuroprotective activities. More importantly, the synergism between these targets might serve as one of the most effective therapeutic strategies to arrest/modify pathological process of AD in addition to improving the cognitive functions for AD.

AB - Alzheimer's disease (AD) is a progressive and degenerative brain disorder that has emerged as one of the major public health problems in adults. Unfortunately, its molecular pathology and therapeutic strategies remain elusive. Because there are multiple factors closely indicated in the pathogenesis of AD, multiple drug therapy will be required to address the varied pathological aspects of this disease. Existing pharmacological approaches with one-molecule-one-target are limited in their ability to modify the pathology of AD. Novel therapeutics strategies comprise multifunctional compounds specifically designed to target concurrently on different sites at multifactorial etiopathogenesis of AD, thereby providing greater therapeutic efficacy. Over the past decade, our group has developed several series of dimeric acetylcholinesterase (AChE) inhibitors derived from tacrine and huperzine A, a unique anti-Alzheimer's drug originally discovered from a traditional Chinese medicinal plant. Bis(7)-Cognitin, one of our novel dimers, through inhibition of AChE, N-methyl-D-aspartate receptor, nitric oxide synthase, and amyloid precursor protein/β-amyloid cascade concurrently, possesses remarkable neuroprotective activities. More importantly, the synergism between these targets might serve as one of the most effective therapeutic strategies to arrest/modify pathological process of AD in addition to improving the cognitive functions for AD.

KW - AChE

KW - Bis(7)-Cognitin

KW - multiple targets

KW - neuroprotection

KW - NMDA receptor

UR - http://www.scopus.com/inward/record.url?scp=57749094960&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57749094960&partnerID=8YFLogxK

U2 - 10.1016/j.nurt.2008.10.040

DO - 10.1016/j.nurt.2008.10.040

M3 - Article

C2 - 19110209

AN - SCOPUS:57749094960

VL - 6

SP - 187

EP - 201

JO - Neurotherapeutics

JF - Neurotherapeutics

SN - 1933-7213

IS - 1

ER -