scholarly journals Current Concepts of Neurodegenerative Mechanisms in Alzheimer’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Kasthuri Bai Magalingam ◽  
Ammu Radhakrishnan ◽  
Ng Shee Ping ◽  
Nagaraja Haleagrahara
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Large Population ◽  
Memory Loss ◽  
Disease Process ◽  
Brain Regions ◽  
Contributing Factors ◽  
Effective Remedy ◽  
And Function

Neurodegenerative diseases are hereditary or sporadic conditions that result in the progressive loss of the structure and function of neurons as well as neuronal death. Although a range of diseases lie under this umbrella term, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common neurodegenerative diseases that affect a large population around the globe. Alzheimer’s disease is characterized by the abnormal accumulation of extracellular amyloid-β plaques and intraneuronal neurofibrillary tangles in brain regions and manifests as a type of dementia in aged individuals that results in memory loss, multiple cognitive abnormalities, and intellectual disabilities that interfere with quality of life. Since the discovery of AD, a wealth of new information has emerged that delineates the causes, mechanisms of disease, and potential therapeutic agents, but an effective remedy to cure the diseases has not been identified yet. This could be because of the complexity of the disease process, as it involves various contributing factors that include environmental factors and genetic predispositions. This review summarizes the current understanding on neurodegenerative mechanisms that lead to the emergence of the pathology of AD.

scholarly journals ADeditome provides the genomic landscape of A-to-I RNA editing in Alzheimer’s disease

2021 ◽  
Author(s):  
Sijia Wu ◽  
Mengyuan Yang ◽  
Pora Kim ◽  
Xiaobo Zhou
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rna Editing ◽  
Memory Loss ◽  
Brain Regions ◽  
Disease Stage ◽  
Mirna Regulation ◽  
Annotation Database ◽  
Functional Annotations ◽  
Genomic Landscape

Abstract A-to-I RNA editing, contributing to nearly 90% of all editing events in human, has been reported to involve in the pathogenesis of Alzheimer’s disease (AD) due to its roles in brain development and immune regulation, such as the deficient editing of GluA2 Q/R related to cell death and memory loss. Currently, there are urgent needs for the systematic annotations of A-to-I RNA editing events in AD. Here, we built ADeditome, the annotation database of A-to-I RNA editing in AD available at https://ccsm.uth.edu/ADeditome, aiming to provide a resource and reference for functional annotation of A-to-I RNA editing in AD to identify therapeutically targetable genes in an individual. We detected 1676 363 editing sites in 1524 samples across nine brain regions from ROSMAP, MayoRNAseq and MSBB. For these editing events, we performed multiple functional annotations including identification of specific and disease stage associated editing events and the influence of editing events on gene expression, protein recoding, alternative splicing and miRNA regulation for all the genes, especially for AD-related genes in order to explore the pathology of AD. Combing all the analysis results, we found 108 010 and 26 168 editing events which may promote or inhibit AD progression, respectively. We also found 5582 brain region-specific editing events with potentially dual roles in AD across different brain regions. ADeditome will be a unique resource for AD and drug research communities to identify therapeutically targetable editing events. Significance: ADeditome is the first comprehensive resource of the functional genomics of individual A-to-I RNA editing events in AD, which will be useful for many researchers in the fields of AD pathology, precision medicine, and therapeutic researches.

Neurodegenerative Diseases: Parkinson’s and Alzheimer’s Diseases

2018 ◽  
Author(s):  
Aviva Ellenstein ◽  
Christina Prather ◽  
Mikhail Kogan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Palliative Care ◽  
Neurodegenerative Diseases ◽  
Brain Metabolism ◽  
Multidisciplinary Care ◽  
Integrative Approach ◽  
Contributing Factors ◽  
Disease Modifying ◽  
Near Future

Neurodegenerative diseases increase in prevalence with aging. This chapter begins with a discussion of Parkinson’s disease. Optimally individualized treatment includes dopaminergic medications, physiotherapy, and multidisciplinary care. Evidence for integrative approaches is limited. Advances in genetics and biomarkers hold promise for subtype-specific, precision treatment in the near future. The second part of this chapter focuses on Alzheimer’s disease. Standard evaluation includes assessment for possible contributing factors that may worsen cognition, and management includes optimizing factors that may improve cognitive function. No disease-modifying medical approaches yet exist, but increasing emphasis on interventions to limit chronic inflammation and optimize brain metabolism remain fundamental in the integrative approach to Alzheimer’s disease. The new metabolic approach first described by Dr. Dale Bredesen is summarized and the importance of multidisciplinary care, with emphasis on early transition to palliative care when appropriate, is reviewed.

scholarly journals Alzheimer’s disease under the purview of Graph Theory Centric Genetic Networks

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Yegnanarayanan Venkatraman ◽  
◽  
Narayanaa Y Krithicaa ◽  
Valentina E. Balas ◽  
Marius M. Balas ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Graph Theory ◽  
Network Theory ◽  
Memory Loss ◽  
Amyloid Plaque ◽  
Brain Regions ◽  
Protein Protein Interaction ◽  
Communication Demands ◽  
The Brain

Notice that the synapsis of brain is a form of communication. As communication demands connectivity, it is not a surprise that "graph theory" is a fastest growing area of research in the life sciences. It attempts to explain the connections and communication between networks of neurons. Alzheimer’s disease (AD) progression in brain is due to a deposition and development of amyloid plaque and the loss of communication between nerve cells. Graph/network theory can provide incredible insights into the incorrect wiring leading to memory loss in a progressive manner. Network in AD is slanted towards investigating the intricate patterns of interconnections found in the pathogenesis of brain. Here, we see how the notions of graph/network theory can be prudently exploited to comprehend the Alzheimer’s disease. We begin with introducing concepts of graph/network theory as a model for specific genetic hubs of the brain regions and cellular signalling. We begin with a brief introduction of prevalence and causes of AD followed by outlining its genetic and signalling pathogenesis. We then present some of the network-applied outcome in assessing the disease-signalling interactions, signal transduction of protein-protein interaction, disturbed genetics and signalling pathways as compelling targets of pathogenesis of the disease.

C-terminal inhibition of tau assembly in vitro and in Alzheimer's disease

2000 ◽  
Vol 113 (21) ◽  
pp. 3737-3745 ◽  
Author(s):  
A. Abraha ◽  
N. Ghoshal ◽  
T.C. Gamblin ◽  
V. Cryns ◽  
R.W. Berry ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amino Acids ◽  
Disease Process ◽  
Brain Regions ◽  
Microtubule Binding ◽  
C Terminus ◽  
Microtubule Binding Domain ◽  
Tau Polymerization

Alzheimer's disease (AD) is, in part, defined by the polymerization of tau into paired helical and straight filaments (PHF/SFs) which together comprise the fibrillar pathology in degenerating brain regions. Much of the tau in these filaments is modified by phosphorylation. Additionally, a subset also appears to be proteolytically truncated, resulting in the removal of its C terminus. Antibodies that recognize tau phosphorylated at S(396/404)or truncated at E(391) do not stain control brains but do stain brain sections very early in the disease process. We modeled these phosphorylation and truncation events by creating pseudo-phosphorylation and deletion mutants derived from a full-length recombinant human tau protein isoform (ht40) that contains N-terminal exons 2 and 3 and all four microtubule-binding repeats. In vitro assembly experiments demonstrate that both modifications greatly enhance the rates of tau filament formation and that truncation increases the mass of polymer formed, as well. Removal of as few as 12 or as many as 121 amino acids from the C terminus of tau greatly increases the rate and extent of tau polymerization. However, deletion of an additional 7 amino acids, (314)DLSKVTS(320), from the third microtubule-binding repeat results in the loss of tau's ability to form filaments in vitro. These results suggest that only part of the microtubule-binding domain (repeats 1, 2 and a small portion of 3) is crucial for tau polymerization. Moreover, the C terminus of tau clearly inhibits the assembly process; this inhibition can be partially reversed by site-specific phosphorylation and completely removed by truncation events at various sites from S(320) to the end of the molecule.

scholarly journals β-Amyloid is Associated with Aberrant Metabolic Connectivity in Subjects with Mild Cognitive Impairment

2014 ◽  
Vol 34 (7) ◽  
pp. 1169-1179 ◽  
Author(s):  
Felix Carbonell ◽  
Arnaud Charil ◽  
Alex P Zijdenbos ◽  
Alan C Evans ◽  
Barry J Bedell ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Disease Process ◽  
Brain Regions ◽  
Apoe Ε4 ◽  
Positron Emission ◽  
Β Amyloid ◽  
Glucose Hypometabolism

Positron emission tomography (PET) studies using [18F]2-fluoro-2-deoxyglucose (FDG) have identified a well-defined pattern of glucose hypometabolism in Alzheimer's disease (AD). The assessment of the metabolic relationship among brain regions has the potential to provide unique information regarding the disease process. Previous studies of metabolic correlation patterns have demonstrated alterations in AD subjects relative to age-matched, healthy control subjects. The objective of this study was to examine the associations between β-amyloid, apolipoprotein ε4 (APOE ε4) genotype, and metabolic correlations patterns in subjects diagnosed with mild cognitive impairment (MCI). Mild cognitive impairment subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were categorized into β-amyloid-low and β-amyloid-high groups, based on quantitative analysis of [18F]florbetapir PET scans, and APOE ε4 non-carriers and carriers based on genotyping. We generated voxel-wise metabolic correlation strength maps across the entire cerebral cortex for each group, and, subsequently, performed a seed-based analysis. We found that the APOE ε4 genotype was closely related to regional glucose hypometabolism, while elevated, fibrillar β-amyloid burden was associated with specific derangements of the metabolic correlation patterns.

scholarly journals Potential Roles of Sestrin2 in Alzheimer’s Disease: Antioxidation, Autophagy Promotion, and Beyond

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1308
Author(s):  
Shang-Der Chen ◽  
Jenq-Lin Yang ◽  
Yi-Heng Hsieh ◽  
Tsu-Kung Lin ◽  
Yi-Chun Lin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Memory Loss ◽  
Oxygen Species ◽  
Mechanistic Target Of Rapamycin ◽  
Cell Cycle Reentry ◽  
Age Related ◽  
Reduce Activity

Alzheimer's disease (AD) is the most common age-related neurodegenerative disease. It presents with progressive memory loss, worsens cognitive functions to the point of disability, and causes heavy socioeconomic burdens to patients, their families, and society as a whole. The underlying pathogenic mechanisms of AD are complex and may involve excitotoxicity, excessive generation of reactive oxygen species (ROS), aberrant cell cycle reentry, impaired mitochondrial function, and DNA damage. Up to now, there is no effective treatment available for AD, and it is therefore urgent to develop an effective therapeutic regimen for this devastating disease. Sestrin2, belonging to the sestrin family, can counteract oxidative stress, reduce activity of the mammalian/mechanistic target of rapamycin (mTOR), and improve cell survival. It may therefore play a crucial role in neurodegenerative diseases like AD. However, only limited studies of sestrin2 and AD have been conducted up to now. In this article, we discuss current experimental evidence to demonstrate the potential roles of sestrin2 in treating neurodegenerative diseases, focusing specifically on AD. Strategies for augmenting sestrin2 expression may strengthen neurons, adapting them to stressful conditions through counteracting oxidative stress, and may also adjust the autophagy process, these two effects together conferring neuronal resistance in cases of AD.

scholarly journals Characterization of mitochondrial DNA quantity and quality in the human aged and Alzheimer's disease brain

2021 ◽  
Author(s):  
Hans-Ulrich Klein ◽  
Caroline Trumpff ◽  
Hyun-Sik Yang ◽  
Annie J Lee ◽  
Martin Picard ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dna ◽  
Human Brain ◽  
Neurodegenerative Diseases ◽  
Late Onset ◽  
Multivariable Analysis ◽  
Amyloid Β ◽  
Brain Regions ◽  
Mtdna Copy Number

Mitochondrial dysfunction is a feature of neurodegenerative diseases, including Alzheimer's disease (AD). Using whole-genome sequencing, we assessed mitochondrial DNA (mtDNA) heteroplasmy levels and mtDNA copy number (mtDNAcn) in 1,361 human brain samples of five brain regions from three studies. Multivariable analysis of ten common brain pathologies identified tau pathology in the dorsolateral prefrontal cortex and TDP-43 pathology in the posterior cingulate cortex as primary drivers of reduced mtDNAcn in the aged human brain. Amyloid-β pathology, age, and sex were not associated with mtDNAcn. Further, there is evidence for a direct effect of mitochondrial health on cognition. In contrast, while mtDNA heteroplasmy levels increase by about 1.5% per year of life in the cortical regions, we found little evidence for an association with brain pathologies or cognitive functioning. Thus, our data indicates that mtDNA heteroplasmy burden is unlikely to be involved in the pathogenesis of late-onset neurodegenerative diseases.

scholarly journals Baicalein Inhibits Heparin-induced Tau Aggregation by Initializing Tau Oligomer Formation 

2020 ◽  
Author(s):  
Shweta K Sonawane ◽  
Vladimir N Uversky ◽  
Subashchandrabose Chinnathambi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Intrinsically Disordered Proteins ◽  
Senile Plaques ◽  
Memory Loss ◽  
Disordered Proteins ◽  
Protein Accumulation ◽  
Scutellaria Baicalensis Georgi ◽  
Intrinsically Disordered

Abstract BackgroundAmyloid aggregate deposition is the key feature of Alzheimer’s disease. The proteinaceous aggregates found in the afflicted brain are the intra-neuronal neurofibrillary tangles formed by the microtubule-associated protein Tau and extracellular deposits, senile plaques, of amyloid beta (Aβ) peptide proteolytically derived from the amyloid precursor protein. Accumulation of these aggregates has manifestations in the later stages of the disease, such as memory loss and cognitive inabilities originating from the neuronal dysfunction, neurodegeneration, and brain atrophy. Treatment of this disease at the late stages is difficult, and many clinical trials have failed. Hence, the goal is to find means capable of preventing the aggregation of these intrinsically disordered proteins by inhibiting the early stages of their pathological transformations. Polyphenols are known to be neuroprotective agents with the noticeable potential against many neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and Prion diseases. MethodsWe analyzed the capability of Baicalein to inhibit aggregation of human Tau protein by a multifactorial analysis that included several biophysical and biochemical techniques. ResultsThe potency of baicalein, a polyphenol from the Scutellaria baicalensis Georgi, against many neurodegenerative diseases has been screened and validated. ThS fluorescence assay revealed the potent inhibitory activity of Baicalein, whereas ANS revealed its mechanism of Tau inhibition viz. by oligomer capture and dissociation. In addition, Baicalein dissolved the preformed mature fibrils of Tau thereby possessing a dual target action. Tau oligomers formed by Baicalein were non-toxic to neuronal cells, highlighting its role as a potent molecule to be screened against AD. ConclusionIn conclusion, Baicalein inhibits aggregation of hTau40 by enhancing the formation of SDS-stable oligomers and preventing fibril formation. Baicalein-induced oligomers do not affect the viability of the neuroblastoma cells. Therefore, Baicalein can be considered as a lead molecule against Tau pathology in AD.

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 Analysis on Stem cell Treatment of Alzheimer's Disease

2021 ◽  
Vol 271 ◽  
pp. 03072
Author(s):  
Weixun Zhu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Neurodegenerative Diseases ◽  
Cell Transplantation ◽  
Memory Loss ◽  
Cell Therapies ◽  
Stem Cell Treatment

Alzheimer's disease is a neurodegenerative disease characterized by progressive memory loss and cognitive impairment. At present, conventional drugs have little effect on the prevention and treatment of AD, and the rapidly developing stem cell transplantation therapy provides a new direction for the treatment of neurodegenerative diseases. In this paper, we can conclude that stem cell therapies such as neural stem cells and mesenchymal stem cells have shown curative effects in the treatment of neurodegenerative diseases such as Alzheimer’s disease by analyzing existing stem cell research and analysis at this stage, and there will be huge applications in the future. prospect. Stem cells can secrete immunoregulatory factors through paracrine pathways to inhibit inflammation and reduce the accumulation of amyloid. Secrete neurotrophic factors to protect and promote nerve growth. In addition, stem cells can differentiate into neurons after transplantation, replacing damaged and dead nerve cells, and play an important role in rebuilding brain neural circuits and networks. This article analyzes and summarizes the possible ways of stem cell transplantation to treat Alzheimer's disease, which can provide new ideas and methods for future stem cell transplantation therapies.

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