scholarly journals Complement System in Alzheimer’s Disease

2021 ◽  
Vol 22 (24) ◽  
pp. 13647
Author(s):  
Akash Shah ◽  
Uday Kishore ◽  
Abhishek Shastri
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Complement System ◽  
Short Term Memory ◽  
Neurodegenerative Disorder ◽  
Membrane Attack Complex ◽  
Future Research ◽  
Chronic Neuroinflammation ◽  
The Central Nervous System ◽  
The Complement System

Alzheimer’s disease is a type of dementia characterized by problems with short-term memory, cognition, and difficulties with activities of daily living. It is a progressive, neurodegenerative disorder. The complement system is an ancient part of the innate immune system and comprises of more than thirty serum and membrane-bound proteins. This system has three different activating pathways and culminates into the formation of a membrane attack complex that ultimately causes target cell lysis (usually pathogens) The complement system is involved in several important functions in the central nervous system (CNS) that include neurogenesis, synaptic pruning, apoptosis, and neuronal plasticity. Here, we discuss how the complement system is involved in the effective functioning of CNS, while also contributing to chronic neuroinflammation leading to neurodegenerative disorders such as Alzheimer’s disease. We also discuss potential targets in the complement system for stopping its harmful effects via neuroinflammation and provide perspective for the direction of future research in this field.

Hunting for biomarkers: The complement system in Alzheimer's disease

Immunobiology ◽  
2012 ◽  
Vol 217 (11) ◽  
pp. 1175
Author(s):  
Svetlana Hakobyan ◽  
Mohammed Aiyaz ◽  
Alexandra Stretton ◽  
Martina Sattlecker ◽  
Richard Dobson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Complement System ◽  
The Complement System

scholarly journals Prostacyclin Promotes Degenerative Pathology in a Model of Alzheimer’s disease

2020 ◽  
Author(s):  
Tasha R. Womack ◽  
Craig Vollert ◽  
Odochi Nwoko ◽  
Monika Schmitt ◽  
Sagi Montazari ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Amyloid Β ◽  
Chronic Neuroinflammation ◽  
Model Of Alzheimer’S Disease ◽  
Amyloid Accumulation ◽  
Prostaglandin H ◽  
The Brain

AbstractAlzheimer’s disease (AD) is a progressive neurodegenerative disorder that is the most common cause of dementia in aged populations. A substantial amount of data demonstrates that chronic neuroinflammation can accelerate neurodegenerative pathologies, while epidemiological and experimental evidence suggests that the use of anti-inflammatory agents may be neuroprotective. In AD, chronic neuroinflammation results in the upregulation of cyclooxygenase and increased production of prostaglandin H2, a precursor for many vasoactive prostanoids. While it is well-established that many prostaglandins can modulate the progression of neurodegenerative disorders, the role of prostacyclin (PGI2) in the brain is poorly understood. We have conducted studies to assess the effect of elevated prostacyclin biosynthesis in a mouse model of AD. Upregulated prostacyclin expression significantly worsened multiple measures associated with amyloid disease pathologies. Mice overexpressing both amyloid and PGI2 exhibited impaired learning and memory and increased anxiety-like behavior compared with non-transgenic and PGI2 control mice. PGI2 overexpression accelerated the development of amyloid accumulation in the brain and selectively increased the production of soluble amyloid-β 42. PGI2 damaged the microvasculature through alterations in vascular length and branching; amyloid expression exacerbated these effects. Our findings demonstrate that chronic prostacyclin expression plays a novel and unexpected role that hastens the development of the AD phenotype.

scholarly journals Potential Role of Phenolic Extracts of Mentha in Managing Oxidative Stress and Alzheimer’s Disease

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 631
Author(s):  
Doaa M. Hanafy ◽  
Geoffrey E. Burrows ◽  
Paul D. Prenzler ◽  
Rodney A. Hill
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Potential Role ◽  
The Elderly ◽  
Future Research ◽  
Phenolic Constituents ◽  
The Central Nervous System ◽  
Developed Nations

With an increase in the longevity and thus the proportion of the elderly, especially in developed nations, there is a rise in pathological conditions that accompany ageing, such as neurodegenerative disorders. Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive and memory decline. The pathophysiology of the disease is poorly understood, with several factors contributing to its development, such as oxidative stress, neuroinflammation, cholinergic neuronal apoptotic death, and the accumulation of abnormal proteins in the brain. Current medications are only palliative and cannot stop or reverse the progression of the disease. Recent clinical trials of synthetic compounds for the treatment of AD have failed because of their adverse effects or lack of efficacy. Thus, there is impetus behind the search for drugs from natural origins, in addition to the discovery of novel, conventional therapeutics. Mints have been used traditionally for conditions relevant to the central nervous system. Recent studies showed that mint extracts and/or their phenolic constituents have a neuroprotective potential and can target multiple events of AD. In this review, we provide evidence of the potential role of mint extracts and their derivatives as possible sources of treatments in managing AD. Some of the molecular pathways implicated in the development of AD are reviewed, with focus on apoptosis and some redox pathways, pointing to mechanisms that may be modulated for the treatment of AD, and the need for future research invoking knowledge of these pathways is highlighted.

Phosphorylation and Glycosylation of Amyloid-β Protein Precursor: The Relationship to Trafficking and Cleavage in Alzheimer’s Disease

2021 ◽  
pp. 1-21
Author(s):  
Xi-Jun Song ◽  
He-Yan Zhou ◽  
Yu-Ying Sun ◽  
Han-Chang Huang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Protein Precursor ◽  
Β Protein ◽  
Cleavage Enzyme ◽  
The Central Nervous System

Alzheimer’s disease (AD) is a neurodegenerative disorder in the central nervous system, and this disease is characterized by extracellular senile plaques and intracellular neurofibrillary tangles. Amyloid-β (Aβ) peptide is the main constituent of senile plaques, and this peptide is derived from the amyloid-β protein precursor (AβPP) through the successive cleaving by β-site AβPP-cleavage enzyme 1 (BACE1) and γ-secretase. AβPP undergoes the progress of post-translational modifications, such as phosphorylation and glycosylation, which might affect the trafficking and the cleavage of AβPP. In the recent years, about 10 phosphorylation sites of AβPP were identified, and they play complex roles in glycosylation modification and cleavage of AβPP. In this article, we introduced the transport and the cleavage pathways of AβPP, then summarized the phosphorylation and glycosylation sites of AβPP, and further discussed the links and relationship between phosphorylation and glycosylation on the pathways of AβPP trafficking and cleavage in order to provide theoretical basis for AD research.

scholarly journals Amyloidosis in Alzheimer’s Disease: The Toxicity of Amyloid Beta (Aβ), Mechanisms of Its Accumulation and Implications of Medicinal Plants for Therapy

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Anchalee Prasansuklab ◽  
Tewin Tencomnao
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Herbal Medicines ◽  
Underlying Disease ◽  
Current Therapy ◽  
The Central Nervous System ◽  
Number Of Individuals

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that leads to memory deficits and death. While the number of individuals with AD is rising each year due to the longer life expectancy worldwide, current therapy can only somewhat relieve the symptoms of AD. There is no proven medication to cure or prevent the disease, possibly due to a lack of knowledge regarding the molecular mechanisms underlying disease pathogenesis. Most previous studies have accepted the “amyloid hypothesis,” in which the neuropathogenesis of AD is believed to be triggered by the accumulation of the toxic amyloid beta (Aβ) protein in the central nervous system (CNS). Lately, knowledge that may be critical to unraveling the hidden pathogenic pathway of AD has been revealed. This review concentrates on the toxicity of Aβand the mechanism of accumulation of this toxic protein in the brain of individuals with AD and also summarizes recent advances in the study of these accumulation mechanisms together with the role of herbal medicines that could facilitate the development of more effective therapeutic and preventive strategies.

scholarly journals Zinc transporters in Alzheimer’s disease

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Yingshuo Xu ◽  
Guiran Xiao ◽  
Li Liu ◽  
Minglin Lang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Critical Role ◽  
Zinc Transporters ◽  
Protein Levels ◽  
Zinc Chelator ◽  
The Central Nervous System ◽  
Novel Therapeutic Strategies

AbstractAlzheimer’s disease (AD) is the most devastating neurodegenerative disorder. Due to the increase in population and longevity, incidence will triple by the middle of the twenty-first century. So far, no treatment has prevented or reversed the disease. More than 20 years of multidisciplinary studies have shown that brain zinc dyshomeostasis may play a critical role in AD progression, which provides encouraging clues for metal-targeted therapies in the treatment of AD. Unfortunately, the pilot clinical application of zinc chelator and/or ionophore strategy, such as the use of quinoline-based compounds, namely clioquinol and PBT2, has not yet been successful. The emerging findings revealed a list of key zinc transporters whose mRNA or protein levels were abnormally altered at different stages of AD brains. Furthermore, specifically modulating the expression of some of the zinc transporters in the central nervous system through genetic methods slowed down or prevented AD progression in animal models, resulting in significantly improved cognitive performance, movement, and prolonged lifespan. Although the underlying molecular mechanisms are not yet fully understood, it shed new light on the treatment or prevention of the disease. This review considers recent advances regarding AD, zinc and zinc transporters, recapitulating their relationships in extending our current understanding of the disease amelioration effects of zinc transport proteins as potential therapeutic targets to cure AD, and it may also provide new insights to identify novel therapeutic strategies for ageing and other neurodegenerative diseases, such as Huntington’s and Parkinson’s disease.

scholarly journals Epigenetics of Alzheimer’s Disease

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 195
Author(s):  
Matea Nikolac Perkovic ◽  
Alja Videtic Paska ◽  
Marcela Konjevod ◽  
Katarina Kouter ◽  
Dubravka Svob Strac ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Posttranslational Modifications ◽  
Neurodegenerative Disorder ◽  
Current Knowledge ◽  
Current Evidence ◽  
Mtdna Copy Number ◽  
Rna Regulation ◽  
The Central Nervous System

There are currently no validated biomarkers which can be used to accurately diagnose Alzheimer’s disease (AD) or to distinguish it from other dementia-causing neuropathologies. Moreover, to date, only symptomatic treatments exist for this progressive neurodegenerative disorder. In the search for new, more reliable biomarkers and potential therapeutic options, epigenetic modifications have emerged as important players in the pathogenesis of AD. The aim of the article was to provide a brief overview of the current knowledge regarding the role of epigenetics (including mitoepigenetics) in AD, and the possibility of applying these advances for future AD therapy. Extensive research has suggested an important role of DNA methylation and hydroxymethylation, histone posttranslational modifications, and non-coding RNA regulation (with the emphasis on microRNAs) in the course and development of AD. Recent studies also indicated mitochondrial DNA (mtDNA) as an interesting biomarker of AD, since dysfunctions in the mitochondria and lower mtDNA copy number have been associated with AD pathophysiology. The current evidence suggests that epigenetic changes can be successfully detected, not only in the central nervous system, but also in the cerebrospinal fluid and on the periphery, contributing further to their potential as both biomarkers and therapeutic targets in AD.

scholarly journals A review of the mechanisms underlying selected comorbidities in Alzheimer’s disease

2021 ◽  
Author(s):  
Karolina Maciejewska ◽  
Kamila Czarnecka ◽  
Paweł Szymański
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Fatal Outcome ◽  
Significant Risk ◽  
The Elderly ◽  
Therapeutic Strategies ◽  
Rapid Progression ◽  
Mental Deterioration ◽  
The Central Nervous System

AbstractAlzheimer's disease (AD) is a progressive neurodegenerative disorder of the central nervous system (CNS) leading to mental deterioration and devastation, and eventually a fatal outcome. AD affects mostly the elderly. AD is frequently accompanied by hypercholesterolemia, hypertension, atherosclerosis, and diabetes mellitus, and these are significant risk factors of AD. Other conditions triggered by the progression of AD include psychosis, sleep disorders, epilepsy, and depression. One important comorbidity is Down’s syndrome, which directly contributes to the severity and rapid progression of AD. The development of new therapeutic strategies for AD includes the repurposing of drugs currently used for the treatment of comorbidities. A better understanding of the influence of comorbidities on the pathogenesis of AD, and the medications used in its treatment, might allow better control of disease progression, and more effective pharmacotherapy. Graphic abstract

scholarly journals Approaches to Optimizing Dantrolene Neuroprotection for the Treatment of Alzheimer's Disease

2020 ◽  
Vol 17 (4) ◽  
pp. 324-328
Author(s):  
Matan B. Abou ◽  
Liang Sun ◽  
Huafeng Wei
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Memory Loss ◽  
Current Status ◽  
Beneficial Effects ◽  
Incidence And Mortality ◽  
High Incidence ◽  
The Central Nervous System ◽  
Dose Dependent

Alzheimer’s Disease (AD), a neurodegenerative disorder with high incidence and mortality, is leading its way to the top of the list of the deadliest diseases without an effective disease-modifying drug. Ca2+ dysregulation, specifically abnormal release of Ca2+ via over activated ryanodine receptor (RyR), has been increasingly considered as an alternative upstream mechanism in AD pathology. Consequently, dantrolene, a RyR antagonist and FDA approved drug to treat malignant hyperthermia and chronic muscle spasms, has been shown to ameliorate memory loss in AD transgenic mice. However, the inefficiency of dantrolene to pass the Blood Brain Barrier (BBB) and penetrate the Central Nervous System needs to be resolved, considering its dose-dependent neuroprotection in AD and other neurodegenerative diseases. In this mini-review, we will discuss the current status of dantrolene neuroprotection in AD treatment and a strategy to maximize its beneficial effects, such as intranasal administration of dantrolene.

Retinal Changes in Transgenic Mouse Models of Alzheimer’s Disease

2021 ◽  
Vol 18 ◽  
Author(s):  
Li Guo ◽  
Nivedita Ravindran ◽  
Daniel Hill ◽  
M. Francesca Cordeiro
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Neurodegenerative Disorder ◽  
Neuronal Loss ◽  
Immunohistochemical Analysis ◽  
Therapeutic Effects ◽  
The Central Nervous System ◽  
New Treatments ◽  
The Brain

: Alzheimer’s disease (AD) is a neurodegenerative disorder, the most common form of dementia. AD is characterized by amyloid-ß (Aß) plaques and neurofibrillary tangles (NFT) in the brain, in association with neuronal loss and synaptic failure, causing cognitive deficits. Accurate and early diagnosis is currently unavailable in lifespan, hampering early intervention of potential new treatments. Visual deficits have been well-documented in AD patients, and the pathological changes identified in the brain are also believed to be found in the retina, an integral part of the central nervous system. Retinal changes can be detected by real-time non-invasive imaging due to the transparent nature of the ocular media, potentially allowing an earlier diagnosis as well as monitoring disease progression and treatment outcome. Animal models are essential for AD research, and this review has a focus on retinal changes in various transgenic AD mouse models with retinal imaging and immunohistochemical analysis as well as therapeutic effects in those models. We also discuss the limitations of transgenic AD models in clinical translations.

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