Strategic approaches to target the enzymes using natural compounds for the management of Alzheimer’s disease: A review

2021 ◽  
Vol 20 ◽  
Author(s):  
Syed Sayeed Ahmad ◽  
Kaiser Younis ◽  
Jeandet Philippe ◽  
Michael Aschner ◽  
Haroon Khan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Genetic Factors ◽  
Cholesterol Metabolism ◽  
Memory Loss ◽  
Amyloid Plaques ◽  
Natural Compounds ◽  
Neurological Deficits ◽  
Hyperphosphorylated Tau Protein

: Alzheimer's disease (AD) is a chronic neurodegenerative disease. It is clinically characterized by memory loss and intellectual decrease, among other neurological deficits. The etiology of AD is not completely understood but includes amyloid plaques and intracellular helical filaments as well as neurofibrillary tangles with hyperphosphorylated tau protein. AD is also associated with alterations in amyloid processing genes, such as PSEN1 or PSEN2 and APP. The modulation immune system, cholesterol metabolism, and synaptic vesicle endocytosis have all been shown to remediate AD. In this review, enzymes such as AChE, BuChE, β-secretase, γ-secretase, MAO, and RAGE are discussed as potential targets for AD treatment. The aim of this review was to addresses the molecular mechanisms as well as various genetic factors in AD etiology. The use of natural compounds against these targets might be beneficial for the management of AD.

scholarly journals A Global Review on Alzheimer’s Disease

2021 ◽  
Vol 68 (1) ◽  
Author(s):  
Natarajan. P ◽  
Mumthaj. P ◽  
Vijay. J ◽  
Gokul. V
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
Genetic Factors ◽  
Environmental Changes ◽  
Late Onset ◽  
Memory Loss ◽  
Review Article ◽  
Acetyl Cholinesterase ◽  
Alois Alzheimer

Alzheimer’s disease (AD) is an inevitable neurological disorder in which the death of brain cells causes memory loss and cognitive decline and ultimate dementia. It’s the foremost common cause of dementia in people of 65 years and older. It was first described by a neurologist Alois Alzheimer in 1906. This review article gives an account on the various symptoms from pre-dementia to severe Alzheimer’s dementia. The Alzheimer’s disease is caused by the pathogenesis by accumulation of toxic amyloid-? plaques (A?) and Hyper phosphorylated tau (p-tau). The greatest risk factors for late onset Alzheimer’s are age, genetics, family history and non-genetic factors (heart health, life style modifications, and environmental changes). The diagnosis of AD advances in genetics, the event of biomarkers of neuro degeneration and neuroimaging discovery utilizes the method to detect AD. The medication use to treat AD is acetyl cholinesterase inhibitors and N-methyl D aspartate antagonists and various drugs are under clinical trials.

Mechanisms of memory loss in Aβ and tau mouse models

2005 ◽  
Vol 33 (4) ◽  
pp. 591-594 ◽  
Author(s):  
K.H. Ashe
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Mouse Models ◽  
Molecular Mechanisms ◽  
Cultured Cells ◽  
Memory Loss ◽  
Amyloid Β ◽  
Aβ Amyloid ◽  
Mechanisms Of Memory

Although memory loss is the central symptom of Alzheimer's disease, the pathophysiological mechanisms leading to dementia are poorly understood. It is difficult to answer this issue with studies in humans and impossible in cultured cells. Therefore animal models are needed to elucidate the molecular mechanisms leading to dementia. The chief neuropathological changes during Alzheimer's disease, namely neurofibrillary tangles and amyloid plaques, have helped us to determine which molecules to focus upon in the animal models, specifically Aβ (amyloid β) and tau. This paper presents my perspective on what we have learnt about mechanisms of memory loss from Aβ and tau mouse models of Alzheimer's disease.

Alzheimer’s Disease: Causes, Mechanisms, and Steps Toward Prevention

2020 ◽  
Author(s):  
Se Hoon Choi ◽  
Rudolph E. Tanzi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Memory Loss ◽  
The Elderly ◽  
The United States ◽  
Fatal Disease ◽  
Comprehensive Overview ◽  
Total Incidence ◽  
Symptomatic Diagnosis

Alzheimer’s disease (AD) is the most common form of dementia in the elderly; it is clinically characterized by progressive memory loss and catastrophic cognitive dysfunction. Neuropathologically, the brains of AD patients are characterized by abundant beta-amyloid plaques, neurofibrillary tangles, and neuroinflammation. To date, this fatal disease ranks as the sixth leading cause of death; 5.8 million people in the United States are estimated to have the disease, and the total incidence of AD-related dementia is projected to grow to 16 million by 2050. Currently, there is no cure or any reliable means for pre-symptomatic diagnosis of AD. AD is a genetically heterogenous and multifactorial disease, and a variety of molecular mechanisms have been suggested to underlie its etiology and pathogenesis. A better understanding of pathogenic mechanisms underlying the development of AD pathology and symptoms would accelerate the development of effective therapeutic strategies for preventing and treating AD. Here, we present a comprehensive overview of the pathogenetic and molecular mechanisms underlying AD along with current therapeutic and lifestyles interventions being investigated for the prevention and treatment of this devastating neurological disorder.

scholarly journals ROLE OF MITOCHONDRIAL DISFUNCTION IN THE DEVELOPMENT OF ALZHEIMER’S DISEASE

2021 ◽  
Vol 67 (1) ◽  
pp. 57-66
Author(s):  
V.V. Ganzha ◽  
◽  
E.A. Lukyanetz ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Tau Protein ◽  
Mitochondrial Dynamics ◽  
Memory Loss ◽  
Disease Process ◽  
Hyperphosphorylated Tau Protein ◽  
Amyloid Aβ

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory loss and multiple cognitive impairments. Several decades of intensive research have shown that multicellular changes are involved in AD’s development and progression, including mitochondrial damage, synaptic dysfunction, formation and accumulation of beta-amyloid (Aβ), formation and accumulation of hyperphosphorylated tau protein, and loss of neurons in patients with this disease. Among them, mitochondrial dysfunction and synaptic damage are the primary manifestations in the disease process. Recent studies have also shown that defective mitophagy caused by Aβ and tau protein are the main indicators in AD’s pathogenesis. This review includes an overview of recent researches on the role of mitochondria in AD development. The review summarizes several aspects of mitochondrial dysfunction, including abnormal mitochondrial dynamics, changes in mitochondrial DNA, and calcium dyshomeostasis in AD pathogenesis

scholarly journals Body Fluid Biomarkers for Alzheimer’s Disease—An Up-To-Date Overview

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 421 ◽  
Author(s):  
Adrian Florian Bălașa ◽  
Cristina Chircov ◽  
Alexandru Mihai Grumezescu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Amyloid Β ◽  
Amyloid Plaques ◽  
Protein Levels ◽  
Chronic Neuroinflammation ◽  
Complex Process ◽  
Novel Biomarkers ◽  
Underlying Mechanisms

Neurodegeneration is a highly complex process which is associated with a variety of molecular mechanisms related to ageing. Among neurodegenerative disorders, Alzheimer’s disease (AD) is the most common, affecting more than 45 million individuals. The underlying mechanisms involve amyloid plaques and neurofibrillary tangles (NFTs) deposition, which will subsequently lead to oxidative stress, chronic neuroinflammation, neuron dysfunction, and neurodegeneration. The current diagnosis methods are still limited in regard to the possibility of the accurate and early detection of the diseases. Therefore, research has shifted towards the identification of novel biomarkers and matrices as biomarker sources, beyond amyloid-β and tau protein levels within the cerebrospinal fluid (CSF), that could improve AD diagnosis. In this context, the aim of this paper is to provide an overview of both conventional and novel biomarkers for AD found within body fluids, including CSF, blood, saliva, urine, tears, and olfactory fluids.

scholarly journals Potential Therapeutic Approaches to Alzheimer’s Disease By Bioinformatics, Cheminformatics And Predicted Adme-Tox Tools

2020 ◽  
Vol 18 (8) ◽  
pp. 696-719
Author(s):  
Speranta Avram ◽  
Maria Mernea ◽  
Carmen Limban ◽  
Florin Borcan ◽  
Carmen Chifiriuc
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nmda Receptors ◽  
In Silico ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Experimental Studies ◽  
Natural Compounds ◽  
Synthetic Compounds ◽  
Ache Inhibitors

Background: Alzheimer’s disease (AD) is considered a severe, irreversible and progressive neurodegenerative disorder. Currently, the pharmacological management of AD is based on a few clinically approved acethylcholinesterase (AChE) and N-methyl-D-aspartate (NMDA) receptor ligands, with unclear molecular mechanisms and severe side effects. Methods: Here, we reviewed the most recent bioinformatics, cheminformatics (SAR, drug design, molecular docking, friendly databases, ADME-Tox) and experimental data on relevant structurebiological activity relationships and molecular mechanisms of some natural and synthetic compounds with possible anti-AD effects (inhibitors of AChE, NMDA receptors, beta-secretase, amyloid beta (Aβ), redox metals) or acting on multiple AD targets at once. We considered: (i) in silico supported by experimental studies regarding the pharmacological potential of natural compounds as resveratrol, natural alkaloids, flavonoids isolated from various plants and donepezil, galantamine, rivastagmine and memantine derivatives, (ii) the most important pharmacokinetic descriptors of natural compounds in comparison with donepezil, memantine and galantamine. Results: In silico and experimental methods applied to synthetic compounds led to the identification of new AChE inhibitors, NMDA antagonists, multipotent hybrids targeting different AD processes and metal-organic compounds acting as Aβ inhibitors. Natural compounds appear as multipotent agents, acting on several AD pathways: cholinesterases, NMDA receptors, secretases or Aβ, but their efficiency in vivo and their correct dosage should be determined. Conclusion: Bioinformatics, cheminformatics and ADME-Tox methods can be very helpful in the quest for an effective anti-AD treatment, allowing the identification of novel drugs, enhancing the druggability of molecular targets and providing a deeper understanding of AD pathological mechanisms.

scholarly journals The Dual GLP-1/GIP Receptor Agonist DA4-JC Shows Superior Protective Properties Compared to the GLP-1 Analogue Liraglutide in the APP/PS1 Mouse Model of Alzheimer’s Disease

2020 ◽  
Vol 35 ◽  
pp. 153331752095304
Author(s):  
Mark Maskery ◽  
Elizabeth Mary Goulding ◽  
Simon Gengler ◽  
Josefine Ulrikke Melchiorsen ◽  
Mette Marie Rosenkilde ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Receptor Agonist ◽  
Neurodegenerative Disorder ◽  
Memory Loss ◽  
Amyloid Plaques ◽  
Model Of Alzheimer’S Disease ◽  
The Brain ◽  
Gip Receptor

Alzheimer’s disease (AD) is a neurodegenerative disorder for which there is no cure. Here, we test a dual GLP-1/GIP receptor agonist (DA4-JC) that has a cell penetrating sequence added to enhance blood-brain barrier penetration. We show in a receptor activity study that DA4-JC has balanced activity on both GLP-1 and GIP receptors but not on GLP-2 or Glucagon receptors. A dose-response study in the APP/PS1 mouse model of AD showed both a dose-dependent drug effect on the inflammation response and the reduction of amyloid plaques in the brain. When comparing DA4-JC with the GLP-1 analogue liraglutide at equal doses of 10nmol/kg bw ip. once-daily for 8 weeks, DA4-JC was more effective in reversing memory loss, enhancing synaptic plasticity (LTP) in the hippocampus, reducing amyloid plaques and lowering pro-inflammatory cytokine levels in the brain. The results suggest that DA4-JC may be a novel treatment for AD.

scholarly journals Amyloid Plaques of Alzheimer’s Disease as Hotspots of Glutamatergic Activity

2018 ◽  
Vol 25 (4) ◽  
pp. 288-297 ◽  
Author(s):  
Saak V. Ovsepian ◽  
Valerie B. O’Leary ◽  
Laszlo Zaborszky ◽  
Vasilis Ntziachristos ◽  
J. Oliver Dolly
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Loss ◽  
Amyloid Plaques ◽  
Neuronal Function ◽  
Axonal Pathology ◽  
The Impact ◽  
Excitatory Drive ◽  
Axonal Swellings ◽  
Presynaptic Proteins

Deposition of amyloid plaques in limbic and associative cortices is amongst the most recognized histopathologic hallmarks of Alzheimer’s disease. Despite decades of research, there is a lack of consensus over the impact of plaques on neuronal function, with their role in cognitive decline and memory loss undecided. Evidence has emerged suggesting complex and localized axonal pathology around amyloid plaques, with a significant fraction of swellings and dystrophies becoming enriched with putative synaptic vesicles and presynaptic proteins normally colocalized at hotspots of transmitter release. In the absence of hallmark active zone proteins and postsynaptic receptive elements, the axonal swellings surrounding amyloid plaques have been suggested as sites for ectopic release of glutamate, which under reduced clearance can lead to elevated local excitatory drive. Throughout this review, we consider the emerging data suggestive of amyloid plaques as hotspots of compulsive glutamatergic activity. Evidence for local and long-range effects of nonsynaptic glutamate is discussed in the context of circuit dysfunctions and neurodegenerative changes of Alzheimer’s disease.

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