A Pathophysiological and Pharmacological review on Alzheimer’s disease: A Current Need

2021 ◽  
Vol 14 (1) ◽  
pp. 75-80
Author(s):  
D. Sheela ◽  
R. Rohan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Neurofibrillary Tangle ◽  
Novel Therapy ◽  
Detection Techniques ◽  
Herbal Plants ◽  
Ancient Times ◽  
Fluid Levels

Developing countries including India faces major setback in medicine and public health due to the neurodegenerative disorders. Among various neurodegenerative diseases like Parkinsonism, Hunting ton's disorder, Amyotrophic lateral syndrome, Alzheimer's is a usual subtype of dementia which has affected about 25 million people globally in 2000 and this statisticis believed to increase to 114 million in 2050. Aging has been found as one of the factors associated with Alzheimer's disease. Their association was confirmed with an increase in the incidence of this disease. A measure of the main constituent of plaque, cerebrospinal fluid levels of Aβ, and constituent of a neurofibrillary tangle, tau protein are the in-vivo biological markers of Alzheimer's disease patients. From ancient times various herbal plants were used for the treatment of Alzheimer’s. The Pharmacological drugs used were Anticholinesterase, Muscarinic receptor agonist, Glutamate receptor antagonist. The newer monoclonal antibodies were introduced for the treatment but the success rate was merge. Resveratrol, an activator of silent information regulator type1(SIRT1) was the latest drug in treating this neurodegenerative disorder. The multifactorial aetiologies leading to neurodegeneration in Alzheimer's made the treatment more complex. At present, the introduction of novel therapy mainly targeting on the pathophysiology of neuroinflammation mediated by microglia and astrocytes gave a newer insight on Alzheimer's. The determination of biomarkers and newer detection techniques can help in the future for early detection in elderly patients and better pharmacotherapy in this complicated disease.

Electromagnetic field in Alzheimer’s disease: a literature review of recent preclinical and clinical studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Reem Habib Mohamad Ali Ahmad ◽  
Marc Fakhoury ◽  
Nada Lawand
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
In Vivo Studies ◽  
Key Factors ◽  
Potential Benefits ◽  
Preclinical And Clinical Studies ◽  
The Brain

: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloidbeta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

scholarly journals Article Commentary: Alzheimer's Disease, Diagnosis and the Need for Biomarkers

2008 ◽  
Vol 3 ◽  
pp. BMI.S682 ◽  
Author(s):  
Claudie Hooper ◽  
Simon Lovestone ◽  
Ricardo Sainz-Fuertes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Memory Loss ◽  
Cost Effective ◽  
Predictive Biomarker ◽  
Disease Diagnosis ◽  
Response To Therapy ◽  
Histopathological Analysis

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of aging that presents with memory loss, disorientation, confusion and a reduction in cognitive ability. Although a definite diagnosis of the disorder can only be made post-mortem by histopathological analysis, a number of methods are currently available for the in vivo assessment of AD including psycho-metric tests and neuro-imaging. However, these clinical assessments are relatively nonspecific and imaging is very costly. Genetic testing can be performed if familial AD is suspected, although such cases represent a very small minority of total AD cases. Apolipoprotein E genotype provides a measure for analysing the risk of developing AD, but does not act as an absolute predictive biomarker for AD. Therefore there is a need for an accurate, universal, specific and cost-effective biomarker to facilitate not only ante-mortem diagnosis of AD, but also to allow progression of the disease and response to therapy to be monitored. This is the ultimate goal that our group is pursuing through the pan-European AddNeuroMed project.

Xanthone: Potential Acetylcholinesterase Inhibitor for Alzheimer's Disease Treatment

2021 ◽  
Vol 21 ◽  
Author(s):  
Vincentsia Vienna Vanessa ◽  
Siau Hui Mah
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Acetylcholinesterase Inhibitor ◽  
Structure Activity Relationship ◽  
Acetylcholinesterase Inhibition ◽  
Activity Relationship ◽  
Structure Activity ◽  
Hydrophobic Moiety

: Alzheimer's disease is a neurodegenerative disorder that results in progressive and irreversible central nervous system impairment, which has become one of the severe issues recently. The most successful approach of Alzheimer’s treatment is the administration of cholinesterase inhibitors to prevent the hydrolysis of acetylcholine and subsequently improve the cholinergic postsynaptic transmission. This review highlights a class of heterocycle, namely xanthone and its remarkable acetylcholinesterase inhibitory activities. Naturally occurring xanthones, including oxygenated, prenylated, pyrano and glycosylated xanthones exhibited promising inhibition effects towards acetylcholinesterase. Interestingly, synthetic xanthone derivatives with complex substituents such as alkyl, pyrrolidine, piperidine and morpholine have shown greater acetylcholinesterase inhibition activities. Structure-activity relationship of xanthones revealed that the type and position of substituent(s) attached to the xanthone moiety influenced their acetylcholinesterase inhibition activities where hydrophobic moiety will lead to an improved activity by contributing the π-π interactions, as well as the hydroxy substituent(s) by forming hydrogen-bond interactions. Thus, further studies including quantitative structure-activity relationship, in vivo and clinical validation studies are crucial for the development of xanthones into novel anti-Alzheimer's disease drugs.

scholarly journals A Changing Perspective on the Role of Neuroinflammation in Alzheimer's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Donna M. Wilcock
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glial Cells ◽  
Neurofibrillary Tangles ◽  
Neurodegenerative Disorder ◽  
Neurofibrillary Tangle ◽  
Amyloid Plaques ◽  
Published Data ◽  
Amyloid Load ◽  
The Brain

Alzheimer's disease (AD) is a complex, neurodegenerative disorder characterized by the presence of amyloid plaques and neurofibrillary tangles in the brain. Glial cells, particularly microglial cells, react to the presence of the amyloid plaques and neurofibrillary tangles producing an inflammatory response. While once considered immunologically privileged due to the blood-brain barrier, it is now understood that the glial cells of the brain are capable of complex inflammatory responses. This paper will discuss the published literature regarding the diverse roles of neuroinflammation in the modulation of AD pathologies. These data will then be related to the well-characterized macrophage phenotypes. The conclusion is that the glial cells of the brain are capable of a host of macrophage responses, termed M1, M2a, M2b, and M2c. The relationship between these states and AD pathologies remains relatively understudied, yet published data using various inflammatory stimuli provides some insight. It appears that an M1-type response lowers amyloid load but exacerbates neurofibrillary tangle pathology. In contrast, M2a is accompanied by elevated amyloid load and appears to ameliorate, somewhat, neurofibrillary pathology. Overall, it is clear that more focused, cause-effect studies need to be performed to better establish how each inflammatory state can modulate the pathologies of AD.

P.5.a.008 Is depression a neurodegenerative disorder? An in-vivo link between depression, antidepressant action and Alzheimer's disease

2014 ◽  
Vol 24 ◽  
pp. S629
Author(s):  
S. Lopes ◽  
J.M. Bessa ◽  
J. Vaz-Silva ◽  
P. Fernandez-Vizarra ◽  
M. Castelhano-Carlos ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Antidepressant Action

scholarly journals Emerging advances of in vivo detection of chronic traumatic encephalopathy and traumatic brain injury

2019 ◽  
Vol 92 (1101) ◽  
pp. 20180925 ◽  
Author(s):  
Julian D. Dallmeier ◽  
Somayeh Meysami ◽  
David A. Merrill ◽  
Cyrus A. Raji
Keyword(s):  
Early Detection ◽  
Diffusion Mri ◽  
Neurodegenerative Disorder ◽  
Chronic Traumatic Encephalopathy ◽  
Neurofibrillary Tangle ◽  
Detection Methods ◽  
Detection Techniques ◽  
In Vivo Detection ◽  
Neuroimaging Techniques

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder that is of epidemic proportions in contact sports athletes and is linked to subconcussive and concussive repetitive head impacts (RHI). Although postmortem analysis is currently the only confirmatory method to diagnose CTE, there has been progress in early detection techniques of fluid biomarkers as well as in advanced neuroimaging techniques. Specifically, promising new methods of diffusion MRI and radionucleotide PET scans could aid in the early detection of CTE. The authors examine early detection methods focusing on various neuroimaging techniques. Advances in structural and diffusion MRI have demonstrated the ability to measure volumetric and white matter abnormalities associated with CTE. Recent studies using radionucleotides such as flortaucipir and 18F-FDDNP have shown binding patterns that are consistent with the four stages of neurofibrillary tangle (NFT) distribution postmortem. Additional research undertakings focusing on fMRI, MR spectroscopy, susceptibility-weighted imaging, and singlephoton emission CT are also discussed as are advanced MRI methods such as diffusiontensor imaging and arterial spin labeled. Neuroimaging is fast becoming a key instrument in early detection and could prove essential for CTE quantification. This review explores a global approach to in vivo early detection. Limited data of in vivo CTE biomarkers with postmortem confirmation are available. While some data exist, they are limited by selection bias. It is unlikely that a single test will be sufficient to properly diagnosis and distinguish CTE from other neurodegenerative diseases such as Alzheimer disease or Frontotemporal Dementia. However, with a combination of fluid biomarkers, neuroimaging, and genetic testing, early detection may become possible.

303 ESTABLISHMENT OF PREGNANCIES WITH HANDMADE CLONING PORCINE EMBRYOS RECONSTRUCTED WITH FIBROBLASTS CONTAINING AN ALZHEIMER'S DISEASE GENE

2008 ◽  
Vol 20 (1) ◽  
pp. 231 ◽  
Author(s):  
P. M. Kragh ◽  
J. Li ◽  
Y. Du ◽  
L. Lin ◽  
M. Schmidt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Polar Body ◽  
Developmental Competence ◽  
Amyloid Precursor Protein Gene ◽  
Reconstructed Embryos ◽  
Swedish Mutation ◽  
Handmade Cloning

Somatic cell nuclear transfer (SCNT) offers the possibility of pig transgenesis. Importantly, specific genetic manipulations can be performed in donor cells before SCNT to derive pig models for specific human genetic diseases, including the neurodegenerative disorder Alzheimer's disease (AD). In the present study, we established pregnancies after transfer of SCNT blastocysts produced by the handmade cloning (HMC) technique. The blastocysts were transgenic for a human gene, amyloid precursor protein gene with the 'Swedish mutation' (APPsw), causing AD. For transgenesis, minipig fibroblasts were transfected by lipofection with a vector containing the APPsw gene under control of the platelet-derived growth factor β promoter (PDGF-APPsw) and a neomycin-resistance selection gene. Neomycin-resistant colonies were isolated, expanded, analyzed, and used for HMC. Cumulus–oocyte complexes were aspirated from ovaries of slaughtered sows and matured for 41 h. Subsequently, the cumulus cells were removed in hyaluronidase, and zonae pellucidae were partially digested by incubation in pronase. Oocytes with a visible polar body (PB) were subjected to oriented bisection. Less than half of the cytoplasm adjacent to the PB was removed with a microblade. The cytoplasts were used as recipients for embryo reconstruction. Reconstructed embryos were produced by a 2-step fusion procedure. At the first step, 1 cytoplast was fused with 1 fibroblast in the absence of Ca2+. After 1 h, the cytoplast-fibroblast pair and another cytoplast were fused and activated simultaneously in the presence of Ca2+, incubated in cytochalasin B and cycloheximide for 4 h, and then cultured in PZM-3 medium. The development of reconstructed embryos to the blastocysts stage was determined after 5, 6, or 7 days of in vitro culture. To investigate the in vivo developmental capacity, blastocysts were transferred surgically to synchronized recipients. When using PDGF-APPsw-transgenic minipig fibroblasts, the rate of blastocyst formation (mean � SEM) was 39 � 3% (164/424). In comparison, non-transgenic fibroblasts resulted in a blastocyst development of 36 � 7% (36/102). In 4 recipients that received an average of 54 Day 5, 6, and 7 PDGF-APPsw-transgenic blastocysts, 2 ongoing pregnancies were confirmed by ultrasonography, 1 pregnancy was lost, and 1 returned to estrus. The results show a high in vivo developmental competence of blastocysts produced after SCNT of PDGF-APPsw-transgenic minipig fibroblasts.

Breaker peptides against amyloid-β aggregation: a potential therapeutic strategy for Alzheimer’s disease

2021 ◽  
Vol 13 (20) ◽  
pp. 1767-1794
Author(s):  
Nibedita Ghosh ◽  
Lal Mohan Kundu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Amyloid Β ◽  
Unnatural Amino Acid ◽  
General Idea ◽  
In Vivo Studies ◽  
Promising Therapeutic Approach

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, for which blocking the early steps of extracellular misfolded amyloid-β (Aβ) aggregation is a promising therapeutic approach. However, the pathological features of AD progression include the accumulation of intracellular tau protein, membrane-catalyzed cell death and the abnormal deposition of Aβ. Here, we focus on anti-amyloid breaker peptides derived from the Aβ sequence and non-Aβ-based peptides containing both natural and modified amino acids. Critical aspects of the breaker peptides include N-methylation, conformational restriction through cyclization, incorporation of unnatural amino acid, fluorinated molecules, polymeric nanoparticles and PEGylation. This review confers a general idea of such breaker peptides with in vitro and in vivo studies, which may advance our understanding of AD pathology and develop an effective treatment strategy against AD.

scholarly journals Palmitoylethanolamide Dampens Reactive Astrogliosis and Improves Neuronal Trophic Support in a Triple Transgenic Model of Alzheimer’s Disease: In Vitro and In Vivo Evidence

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Maria Rosanna Bronzuoli ◽  
Roberta Facchinetti ◽  
Luca Steardo ◽  
Adele Romano ◽  
Claudia Stecca ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Senile Plaques ◽  
Neuronal Loss ◽  
Adjunct Treatment ◽  
Reactive Astrogliosis ◽  
Model Of Alzheimer’S Disease

Alzheimer’s disease (AD) is a neurodegenerative disorder responsible for the majority of dementia cases in elderly people. It is widely accepted that the main hallmarks of AD are not only senile plaques and neurofibrillary tangles but also reactive astrogliosis, which often precedes detrimental deposits and neuronal atrophy. Such phenomenon facilitates the regeneration of neural networks; however, under some circumstances, like in AD, reactive astrogliosis is detrimental, depriving neurons of the homeostatic support, thus contributing to neuronal loss. We investigated the presence of reactive astrogliosis in 3×Tg-AD mice and the effects of palmitoylethanolamide (PEA), a well-documented anti-inflammatory molecule, by in vitro and in vivo studies. In vitro results revealed a basal reactive state in primary cortical 3×Tg-AD-derived astrocytes and the ability of PEA to counteract such phenomenon and improve viability of 3×Tg-AD-derived neurons. In vivo observations, performed using ultramicronized- (um-) PEA, a formulation endowed with best bioavailability, confirmed the efficacy of this compound. Moreover, the schedule of treatment, mimicking the clinic use (chronic daily administration), revealed its beneficial pharmacological properties in dampening reactive astrogliosis and promoting the glial neurosupportive function. Collectively, our results encourage further investigation on PEA effects, suggesting it as an alternative or adjunct treatment approach for innovative AD therapy.

scholarly journals Resveratrol in Alzheimer's disease: a review of pathophysiology and therapeutic potential

2020 ◽  
Vol 78 (8) ◽  
pp. 501-511 ◽  
Author(s):  
Júlia Canto e SOUSA ◽  
Ana Carolina Fauaze SANTANA ◽  
Gabriela Jesus Prado MAGALHÃES
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Therapeutic Potential ◽  
Senile Plaques ◽  
Cochrane Library ◽  
Original Research ◽  
Protective Effects

ABSTRACT Background: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive and irreversible loss of cognitive function. The presence of senile plaques is one of the pathological markers of the disease and is associated with the onset of neuroinflammatory mechanisms. The exact pathophysiology of AD has not been completely understood, and there are no curative therapies yet. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenol that is noted for its antioxidant and anti-inflammatory properties. Objective: To review the role of resveratrol in the pathophysiological aspects of AD. Methods: This study carried out a literature review using PubMed/Medline, Virtual Health Library (VHL), Web of Sciences, SCOPUS and the Cochrane Library databases. Original research articles, describing both in vitro and in vivo experiments, published between 2008 and 2018, were included. Results: We identified 667 articles, of which 619 were excluded because they were repeated or did not follow the inclusion criteria. The present study includes the remaining 48 articles. Discussion: Resveratrol demonstrates beneficial and protective effects in AD models and seems to provide a promising therapeutic alternative. Conclusion: Although resveratrol appears to mitigate some pathophysiological aspects of AD, further studies are needed to prove the safety and efficacy of this compound in humans.

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