Calcium signalling remodelling and disease

2012 ◽  
Vol 40 (2) ◽  
pp. 297-309 ◽  
Author(s):  
Michael J. Berridge
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Bipolar Disorder ◽  
Cardiac Disease ◽  
Calcium Signalling ◽  
Cell Types ◽  
Wide Range ◽  
Inositol 1,4,5 Trisphosphate ◽  
Different Cell Types ◽  
Signalling Systems

A wide range of Ca2+ signalling systems deliver the spatial and temporal Ca2+ signals necessary to control the specific functions of different cell types. Release of Ca2+ by InsP3 (inositol 1,4,5-trisphosphate) plays a central role in many of these signalling systems. Ongoing transcriptional processes maintain the integrity and stability of these cell-specific signalling systems. However, these homoeostatic systems are highly plastic and can undergo a process of phenotypic remodelling, resulting in the Ca2+ signals being set either too high or too low. Such subtle dysregulation of Ca2+ signals have been linked to some of the major diseases in humans such as cardiac disease, schizophrenia, bipolar disorder and Alzheimer's disease.

Extreme Alleles at the Human Caveolin 1 Gene Novel Purine Complex and Risk of Alzheimer’s Disease

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
M. Ohadi ◽  
Y. Heshmati ◽  
A. Mirabzadeh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorders ◽  
Binding Sites ◽  
Late Onset ◽  
Cell Types ◽  
Structural Protein ◽  
Aberrant Expression ◽  
Caveolin 1 ◽  
Wide Range

Caveolin-1 (CAV1) is the principal structural protein of caveolae membranes that are found in most cell types. Aberrant expression and mutation of this gene are associated with a wide range of disorders including neurodegenerative disorders and various cancers. We report a novel purine complex of three polymorphic motifs located at the enhancer region of the gene and risk of late-onset Alzheimer's disease. Extreme haplotypes with accumulated homozygosity for those haplotypes were observed in the Alzheimer's cases comparing with the controls (p< 0.000). Based on our findings, there is a window of haplotypes and haplotype lengths in the controls. Shorter and longer haplotypes were associated with Alzheimer's disease in our cases.This purine complex contains GGAA and GAAA motifs, the consensus binding sites for the Ets and IRF family transcription factors, respectively, and is highly conserved in distantly-related non-human primates in respect with location and motif sequence. The effect of the extreme haplotypes in the expression of the gene and the pathophysiology of Alzheimer's disease remain to be clarified.

scholarly journals Exosomal miRNAs as Potential Diagnostic Biomarkers in Alzheimer’s Disease

2020 ◽  
Vol 13 (9) ◽  
pp. 243
Author(s):  
Ida Manna ◽  
Selene De Benedittis ◽  
Andrea Quattrone ◽  
Domenico Maisano ◽  
Enrico Iaccino ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Types ◽  
Bioactive Molecules ◽  
Clinical Value ◽  
Rna Sequences ◽  
Exosomal Mirnas ◽  
Preclinical And Clinical Studies ◽  
Internal And External Factors ◽  
Different Cell Types

Alzheimer’s disease (AD), a neurodegenerative disease, is linked to a variety of internal and external factors present from the early stages of the disease. There are several risk factors related to the pathogenesis of AD, among these exosomes and microRNAs (miRNAs) are of particular importance. Exosomes are nanocarriers released from many different cell types, including neuronal cells. Through the transfer of bioactive molecules, they play an important role both in the maintenance of physiological and in pathological conditions. Exosomes could be carriers of potential biomarkers useful for the assessment of disease progression and for therapeutic applications. miRNAs are small noncoding endogenous RNA sequences active in the regulation of protein expression, and alteration of miRNA expression can result in a dysregulation of key genes and pathways that contribute to disease development. Indeed, the involvement of exosomal miRNAs has been highlighted in various neurodegenerative diseases, and this opens the possibility that dysregulated exosomal miRNA profiles may influence AD disease. The advances in exosome-related biomarker detection in AD are summarized. Finally, in this review, we highlight the use of exosomal miRNAs as essential biomarkers in preclinical and clinical studies in Alzheimer’s disease, also taking a look at their potential clinical value.

The Blood brain-barrier and its role in Alzheimer’s disease

Neuroforum ◽  
2018 ◽  
Vol 24 (4) ◽  
pp. A197-A205 ◽  
Author(s):  
Steffen E. Storck ◽  
Claus U. Pietrzik
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Cell Types ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Different Cell Types ◽  
The Brain ◽  
Brain Homeostasis

Abstract The blood brain-barrier (BBB), built up by the interaction of different cell types in vessels of the brain, is essential for brain homeostasis. As a gatekeeper of the central nervous system (CNS), the BBB controls the exchange of molecules between brain and blood. In many neurodegenerative diseases including Alzheimer’s disease (AD) the BBB show alterations which impair brain function and promote neurodegeneration. As an important elimination route for neurotoxic amyloid-beta (Aβ), the BBB is crucial for the healthy brain by regulating the concentration of soluble Aβ in the interstitial fluid (ISF) in the brain. Here, we discuss the composition and distinctive physiological features of CNS vasculature and the pathological alterations that are present in AD and disturb BBB function.

scholarly journals Multi-cellular communities are perturbed in the aging human brain and with Alzheimer’s disease

2020 ◽  
Author(s):  
Anael Cain ◽  
Mariko Taga ◽  
Cristin McCabe ◽  
Idan Hekselman ◽  
Charles C. White ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Cell Types ◽  
Clinicopathologic Characteristics ◽  
Cellular Environment ◽  
Single Nucleus ◽  
Open Question ◽  
Different Cell Types

AbstractThe role of different cell types and their interactions in Alzheimer’s disease (AD) is an open question that we have pursued by mapping the human brain at the single cell level. Here, we present a high resolution cellular map of the aging frontal cortex by single nucleus RNA-sequencing of 24 individuals with different clinicopathologic characteristics; which we used to infer the cellular architecture of 640 individuals from bulk RNA-seq profiles. Powered by this sample of sufficient size to obtain statistically robust results, we uncovered AD associations with neuronal subtypes and oligodendroglial states. Moreover, we uncovered a network of cellular communities, each composed of different neuronal, glial and endothelial cells subpopulations whose frequencies are correlated across individuals. Two of the cellular communities are altered in relation to cognitive decline and tau pathology. Our work provides a roadmap for evaluating cross-cell type differences in the cellular environment of the AD brain.

Therapeutic Properties of Several Chemical Compounds from Salvia officinalis L. in Alzheimer’s Disease

2020 ◽  
Vol 21 ◽  
Author(s):  
Georgiana Uță ◽  
Denisa Ștefania Manolescu ◽  
Speranța Avram
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Side Effects ◽  
Chemical Compounds ◽  
Natural Compounds ◽  
Salvia Officinalis ◽  
Chemical Structures ◽  
In Silico Studies ◽  
Wide Range ◽  
Salvia Officinalis L

Background.: Currently, the pharmacological management in Alzheimer's disease is based on several chemical structures, represented by acetylcholinesterase and N-methyl-D-aspartate (NMDA) receptor ligands, with still unclear molecular mechanisms, but severe side effects. For this reason, a challenge for Alzheimer's disease treatment remains to identify new drugs with reduced side effects. Recently, the natural compounds, in particular certain chemical compounds identified in the essential oil of peppermint, sage, grapes, sea buckthorn, have increased interest as possible therapeutics. Objectives.: In this paper, we have summarized data from the recent literature, on several chemical compounds extracted from Salvia officinalis L., with therapeutic potential in Alzheimer's disease. Methods.: In addition to the wide range of experimental methods performed in vivo and in vitro, also we presented some in silico studies of medicinal compounds. Results. Through this mini-review, we present the latest information regarding the therapeutic characteristics of natural compounds isolated from Salvia officinalis L. in Alzheimer's disease. Conclusion.: Thus, based on the information presented, we can say that phytotherapy is a reliable therapeutic method in a neurodegenerative disease.

scholarly journals NLRP3 Inflammasome: A Starring Role in Amyloid-β- and Tau-Driven Pathological Events in Alzheimer’s Disease

2021 ◽  
pp. 1-22
Author(s):  
Mariana Van Zeller ◽  
Diogo M. Dias ◽  
Ana M. Sebastião ◽  
Cláudia A. Valente
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glial Cells ◽  
Neurofibrillary Tangles ◽  
Nlrp3 Inflammasome ◽  
Neuronal Death ◽  
Inflammatory Responses ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Wide Range

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease commonly diagnosed among the elderly population. AD is characterized by the loss of synaptic connections, neuronal death, and progressive cognitive impairment, attributed to the extracellular accumulation of senile plaques, composed by insoluble aggregates of amyloid-β (Aβ) peptides, and to the intraneuronal formation of neurofibrillary tangles shaped by hyperphosphorylated filaments of the microtubule-associated protein tau. However, evidence showed that chronic inflammatory responses, with long-lasting exacerbated release of proinflammatory cytokines by reactive glial cells, contribute to the pathophysiology of the disease. NLRP3 inflammasome (NLRP3), a cytosolic multiprotein complex sensor of a wide range of stimuli, was implicated in multiple neurological diseases, including AD. Herein, we review the most recent findings regarding the involvement of NLRP3 in the pathogenesis of AD. We address the mechanisms of NLRP3 priming and activation in glial cells by Aβ species and the potential role of neurofibrillary tangles and extracellular vesicles in disease progression. Neuronal death by NLRP3-mediated pyroptosis, driven by the interneuronal tau propagation, is also discussed. We present considerable evidence to claim that NLRP3 inhibition, is undoubtfully a potential therapeutic strategy for AD.

Immune modulations and immunotherapies for Alzheimer’s disease: a comprehensive review

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Sara Mahdiabadi ◽  
Sara Momtazmanesh ◽  
George Perry ◽  
Nima Rezaei
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Cognitive Outcomes ◽  
Tau Proteins ◽  
Causal Role ◽  
Wide Range ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Immune Related Genes

Abstract Alzheimer’s disease (AD), the most common cause of dementia, is characterized by progressive cognitive and memory impairment ensued from neuronal dysfunction and eventual death. Intraneuronal deposition of tau proteins and extracellular senile amyloid-β plaques have ruled as the supreme postulations of AD for a relatively long time, and accordingly, a wide range of therapeutics, especially immunotherapies have been implemented. However, none of them resulted in significant positive cognitive outcomes. Especially, the repetitive failure of anti-amyloid therapies proves the inefficiency of the amyloid cascade hypothesis, suggesting that it is time to reconsider this hypothesis. Thus, for the time being, the focus is being shifted to neuroinflammation as a third core pathology in AD. Neuroinflammation was previously considered a result of the two aforementioned phenomena, but new studies suggest that it might play a causal role in the pathogenesis of AD. Neuroinflammation can act as a double-edged sword in the pathogenesis of AD, and the activation of glial cells is indispensable for mediating such attenuating or detrimental effects. The association of immune-related genes polymorphisms with the clinical phenotype of AD as well as the protective effect of anti-inflammatory drugs like nonsteroidal anti-inflammatory drugs supports the possible causal role of neuroinflammation in AD. Here, we comprehensively review immune-based therapeutic approaches toward AD, including monoclonal antibodies and vaccines. We also discuss their efficacy and underlying reasons for shortcomings. Lastly, we highlight the capacity of modulating the neuroimmune interactions and targeting neuroinflammation as a promising opportunity for finding optimal treatments for AD.

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