Pharmacological Treatment of Alzheimer Disease

Massoud, Fadi; Léger, Gabriel C.

doi:10.1177/070674371105601003

Cited by 98 publications

(67 citation statements)

References 108 publications

(114 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

mentioning

confidence: 99%

mentioning

confidence: 99%

“…4 Despite the huge demand for treatments, existing drugs have limited or no efficacy for AD. 5,6 AD is characterized by a significant loss of neurons and atrophy of the hippocampus and cerebral cortex.7 It begins as mild short-term memory disturbances and ends in total loss of cognition and executive functions.8−10 The neuropathology of AD is characterized by two pathogenic hallmarks: the intraneuronal neurofibrillary tangle (NFT) and the extracellular amyloid plaque. 11,12 NFTs are largely composed of hyperphosphorylated fibrillar forms of a protein called microtubule associated protein tau which accumulates in the entorhinal cortex and the pyramidal neurons of the CA1 region of the hippocampus and subiculum.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Role of ABC Transporters in the Pathogenesis of Alzheimer’s Disease

Abuznait

Kaddoumi

2012

ACS Chem. Neurosci.

110

View full text Add to dashboard Cite

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of age-related dementia that begins with memory loss and progresses to include severe cognitive impairment. A major pathological hallmark of AD is the accumulation of beta amyloid peptide (Aβ) in senile plaques in the brain of AD patients. The exact mechanism by which AD takes place remains unknown. However, an increasing number of studies suggests that ATP-binding cassette (ABC) transporters, which are localized on the surface of brain endothelial cells of the bloodbrain barrier (BBB) and brain parenchyma, may contribute to the pathogenesis of AD. Recent studies have unraveled important roles of ABC transporters including ABCB1 (P-glycoprotein, P-gp), ABCG2 (breast cancer resistant protein, BCRP), ABCC1 (multidrug resistance protein 1, MRP1), and the cholesterol transporter ABCA1 in the pathogenesis of AD and Aβ peptides deposition inside the brain. Therefore, understanding the mechanisms by which these transporters contribute to Aβ deposition in the brain is important for the development of new therapeutic strategies against AD. This review summarizes and highlights the accumulating evidence in the literature which describe the role of altered function of various ABC transporters in the pathogenesis and progression of AD and the implications of modulating their functions for the treatment of AD. KEYWORDS: ABC transporters, Alzheimer's disease, blood-brain barrier, ABCA1, P-glycoprotein, MRP1, BCRP A lzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of age-related dementia that begins with memory loss and progresses to include severe cognitive impairment.1 The pathogenesis of AD is complex, and involves molecular, genetic, cellular, and physiological alterations to the brain and blood-brain barrier (BBB) that are still not completely understood.2,3 The prevalence of AD is going up rapidly worldwide, with about 30 million people suffering from this disease nowadays, and it has an increasing socioeconomic impact. 4 Despite the huge demand for treatments, existing drugs have limited or no efficacy for AD. 5,6 AD is characterized by a significant loss of neurons and atrophy of the hippocampus and cerebral cortex.7 It begins as mild short-term memory disturbances and ends in total loss of cognition and executive functions.8−10 The neuropathology of AD is characterized by two pathogenic hallmarks: the intraneuronal neurofibrillary tangle (NFT) and the extracellular amyloid plaque. 11,12 NFTs are largely composed of hyperphosphorylated fibrillar forms of a protein called microtubule associated protein tau which accumulates in the entorhinal cortex and the pyramidal neurons of the CA1 region of the hippocampus and subiculum.7 The well-known amyloid cascade hypothesis suggests that AD is precipitated by the accumulation of amyloid plaques that are mainly composed of fibrils of peptides collectively known as beta amyloid (Aβ) which are produced by the sequential cleavage of am...

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Role of ABC Transporters in the Pathogenesis of Alzheimer’s Disease

Abuznait

Kaddoumi

2012

ACS Chem. Neurosci.

110

View full text Add to dashboard Cite

show abstract

“…112 The current pharmacological approach to AD treatment is based on vascular prevention and symptomatic therapy with cholinesterase inhibitors and N-methyl-d-aspartate (NMDA) antagonists. 113 Cholinesterase inhibitors are included in drugs such as donepezil, rivastigmine, galantamine, 113 and tacrine. 114 These drugs act by inhibiting the action of AChE and optimizing the levels of acetylcholine available for postsynaptic stimulation.…”

mentioning

confidence: 99%

Nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease

Fonseca-Santos¹,

Chorilli²,

Gremião³

2015

IJN

248

160

View full text Add to dashboard Cite

Alzheimer’s disease is a neurological disorder that results in cognitive and behavioral impairment. Conventional treatment strategies, such as acetylcholinesterase inhibitor drugs, often fail due to their poor solubility, lower bioavailability, and ineffective ability to cross the blood–brain barrier. Nanotechnological treatment methods, which involve the design, characterization, production, and application of nanoscale drug delivery systems, have been employed to optimize therapeutics. These nanotechnologies include polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, and liquid crystals. Each of these are promising tools for the delivery of therapeutic devices to the brain via various routes of administration, particularly the intranasal route. The objective of this study is to present a systematic review of nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease.

show abstract

“…6,7) The cholinergic hypothesis is one of the oldest and most popular hypotheses outlining the pathogenesis of AD. Acetylcholine (ACh) deficiency severely affects the cognitive abilities, memory function and emotional responses in AD patients.…”

mentioning

confidence: 99%

Microwave-Assisted Synthesis, Molecular Docking, and Cholinesterase Inhibitory Activities of New Ethanediamide and 2-Butenediamide Analogues

Koca

Yerdelen

Anil

et al. 2015

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

A novel series of meta-substituted ethanediamide and 2-butenediamide derivatives were synthesized and tested for their ability to inhibit electric eel acetylcholinesterase (AChE) and equine serum butyrylcholinesterase (BuChE). The synthesized compounds were evaluated against ChE enzymes using the colorimetric method described by Ellman et al. (Biochem. Pharmacol., 7, 1961). It was revealed that some synthesized compounds exhibited high anticholinesterase activity, among which compounds 1f and 2f were the most active inhibitors against BuChE (IC 50 value 1.47 µM) and AChE (IC 50 value 2.09 µM), respectively. Docking simulations revealed that the inhibitors 1f and 2f are capable of simultaneously binding the peripheral anionic site as well as the catalytic anionic site of both ChE enzymes. These derivatives are considered interesting candidates for Alzheimer's disease treatment.

show abstract

Pharmacological Treatment of Alzheimer Disease

Abstract: Objective:To review the different pharmacological approaches to the cognitive, functional, and behavioural manifestations of Alzheimer disease (AD). Methods:We searched and critically analyzed the most recent relevant literature on pharmacological treatment of AD.

Cited by 98 publications

References 108 publications

Role of ABC Transporters in the Pathogenesis of Alzheimer’s Disease

Role of ABC Transporters in the Pathogenesis of Alzheimer’s Disease

Nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease

Microwave-Assisted Synthesis, Molecular Docking, and Cholinesterase Inhibitory Activities of New Ethanediamide and 2-Butenediamide Analogues

Contact Info

Product

Resources

About

Pharmacological Treatment of Alzheimer Disease

Abstract: Objective:To review the different pharmacological approaches to the cognitive, functional, and behavioural manifestations of Alzheimer disease (AD). Methods:We searched and critically analyzed the most recent relevant literature on pharmacological treatment of AD.

Cited by 98 publications

References 108 publications

Role of ABC Transporters in the Pathogenesis of Alzheimer’s Disease

Role of ABC Transporters in the Pathogenesis of Alzheimer’s Disease

Nanotechnology-based drug delivery systems for the treatment of Alzheimer&rsquo;s disease

Microwave-Assisted Synthesis, Molecular Docking, and Cholinesterase Inhibitory Activities of New Ethanediamide and 2-Butenediamide Analogues

Contact Info

Product

Resources

About

Nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease