Does Altered Probability of Real Time Diffusional Collisions of Membrane Molecules Trigger or Delay Alzheimers Disease

Deepak Nair; Shekhar Kedia; Mini Jose

doi:10.22580/iscinotej5.5.3

Does Altered Probability of Real Time Diffusional Collisions of Membrane Molecules Trigger or Delay Alzheimers Disease

iScience Notes ◽

10.22580/iscinotej5.5.3 ◽

2020 ◽

Vol 5 (5) ◽

pp. 1-4

Author(s):

Deepak Nair ◽

Shekhar Kedia ◽

Mini Jose

Keyword(s):

Amyloid Precursor Protein ◽

Neurodegenerative Diseases ◽

Real Time ◽

Time Scale ◽

Product Formation ◽

Molecular Events ◽

Millisecond Time Scale ◽

Stochastic Events ◽

Random Diffusion

Understanding stochastic events that control the molecular events leading to the onset of neurodegenerative diseases such as Alzheimer's Disease (AD) is not well understood. Though the bulk of the attention is attributed to the increased burden of detrimental proteoforms generated by the processing of Amyloid Precursor Protein, there lacks a clear consensus on how the molecular events that control the localization and trafficking contribute to the onset. Here, we discuss emerging evidence that indicate the role of nanoscale compositionality of the membrane and random diffusion at the millisecond time scale that contribute to the onset of AD. We believe that intuitive knowledge of nanobiology controlling the local rates of product formation holds the clue for next-generation therapeutics that might delay or halt the onset of AD.

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Spectroscopic ellipsometry on the millisecond time scale for real‐time investigations of thin‐film and surface phenomena

Review of Scientific Instruments ◽

10.1063/1.1143280 ◽

1992 ◽

Vol 63 (8) ◽

pp. 3842-3848 ◽

Cited By ~ 57

Author(s):

Ilsin An ◽

Y. M. Li ◽

H. V. Nguyen ◽

R. W. Collins

Keyword(s):

Thin Film ◽

Real Time ◽

Spectroscopic Ellipsometry ◽

Time Scale ◽

Surface Phenomena ◽

Millisecond Time Scale

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Preventing Neurodegeneration by Controlling Oxidative Stress: The Role of OXR1

Frontiers in Neuroscience ◽

10.3389/fnins.2020.611904 ◽

2020 ◽

Vol 14 ◽

Author(s):

Michael R. Volkert ◽

David J. Crowley

Keyword(s):

Oxidative Stress ◽

Neurodegenerative Diseases ◽

Stress Resistance ◽

Molecular Level ◽

Neuronal Damage ◽

Gene Products ◽

Oxidative Stress Resistance ◽

Molecular Events ◽

Regulatory Functions

Parkinson’s disease, diabetic retinopathy, hyperoxia induced retinopathy, and neuronal damage resulting from ischemia are among the notable neurodegenerative diseases in which oxidative stress occurs shortly before the onset of neurodegeneration. A shared feature of these diseases is the depletion of OXR1 (oxidation resistance 1) gene products shortly before the onset of neurodegeneration. In animal models of these diseases, restoration of OXR1 has been shown to reduce or eliminate the deleterious effects of oxidative stress induced cell death, delay the onset of symptoms, and reduce overall severity. Moreover, increasing OXR1 expression in cells further increases oxidative stress resistance and delays onset of disease while showing no detectable side effects. Thus, restoring or increasing OXR1 function shows promise as a therapeutic for multiple neurodegenerative diseases. This review examines the role of OXR1 in oxidative stress resistance and its impact on neurodegenerative diseases. We describe the potential of OXR1 as a therapeutic in light of our current understanding of its function at the cellular and molecular level and propose a possible cascade of molecular events linked to OXR1’s regulatory functions.

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The Role of Tau in Neurodegenerative Diseases and Its Potential as a Therapeutic Target

Scientifica ◽

10.6064/2012/796024 ◽

2012 ◽

Vol 2012 ◽

pp. 1-20 ◽

Cited By ~ 32

Author(s):

Michael S. Wolfe

Keyword(s):

Neurodegenerative Diseases ◽

Neurological Disorders ◽

Pathological Feature ◽

Tau Pathology ◽

Gene Encoding ◽

Protein Tau ◽

Molecular Events ◽

Potential Therapeutics ◽

Key Questions

The abnormal deposition of proteins in and around neurons is a common pathological feature of many neurodegenerative diseases. Among these pathological proteins, the microtubule-associated protein tau forms intraneuronal filaments in a spectrum of neurological disorders. The discovery that dominant mutations in theMAPTgene encoding tau are associated with familial frontotemporal dementia strongly supports abnormal tau protein as directly involved in disease pathogenesis. This and other evidence suggest that tau is a worthwhile target for the prevention or treatment of tau-associated neurodegenerative diseases, collectively called tauopathies. However, it is critical to understand the normal biological roles of tau, the specific molecular events that induce tau to become neurotoxic, the biochemical nature of pathogenic tau, the means by which pathogenic tau exerts neurotoxicity, and how tau pathology propagates. Based on known differences between normal and abnormal tau, a number of approaches have been taken toward the discovery of potential therapeutics. Key questions still remain open, such as the nature of the connection between the amyloid-βprotein of Alzheimer’s disease and tau pathology. Answers to these questions should help better understand the nature of tauopathies and may also reveal new therapeutic targets and strategies.

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Role of the Structural Characteristics of Dendrimers in the Manifestation of the Antiamyloid Properties

INEOS OPEN ◽

10.32931/io2018r ◽

2020 ◽

Vol 3 ◽

Author(s):

S. A. Sorokina ◽

◽

Yu. Yu. Stroilova ◽

V. I. Muronets ◽

Z. B. Shifrina ◽

...

Keyword(s):

Neurodegenerative Diseases ◽

Structural Characteristics ◽

Short Review ◽

External Factors ◽

Amyloid Aggregation ◽

Amyloid Proteins ◽

Molecular Parameters ◽

Amyloid Aggregates ◽

Aggregation Processes

Among the compounds able to efficiently inhibit the amyloid aggregation of proteins and decompose the amyloid aggregates that cause neurodegenerative diseases, of particular interest are dendrimers, which represent individual macromolecules with the hypercrosslinked architectures and given molecular parameters. This short review outlines the peculiarities of the antiamyloid activity of dendrimers and discusses the effect of dendrimer structures and external factors on their antiamyloid properties. The potential of application of dendrimers in further investigations on the aggregation processes of amyloid proteins as the compounds that exhibit the remarkable antiamyloid activity is evaluated.

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The Role of Advanced Glycation End Products (AGEs) through the TRPA-1/NRF-2 Activation Pathway in the Neurodegenerative Diseases

10.33015/dominican.edu/2017.bio.05 ◽

2017 ◽

Author(s):

Sana Khateeb

Keyword(s):

Neurodegenerative Diseases ◽

Advanced Glycation End Products ◽

Advanced Glycation ◽

Activation Pathway ◽

Glycation End Products ◽

End Products

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Faculty Opinions recommendation of Motions on the millisecond time scale and multiple conformations of HIV-1 capsid protein: implications for structural polymorphism of CA assemblies.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.715447806.791002805 ◽

2012 ◽

Author(s):

David Cowburn

Keyword(s):

Capsid Protein ◽

Time Scale ◽

Structural Polymorphism ◽

Millisecond Time Scale ◽

Multiple Conformations ◽

Hiv 1

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Involvement of Heme Oxygenase-1 in Neuropsychiatric and Neurodegenerative Diseases

Current Pharmaceutical Design ◽

10.2174/1381612824666180717160623 ◽

2018 ◽

Vol 24 (20) ◽

pp. 2283-2302 ◽

Cited By ~ 9

Author(s):

Vivian B. Neis ◽

Priscila B. Rosa ◽

Morgana Moretti ◽

Ana Lucia S. Rodrigues

Keyword(s):

Neurodegenerative Diseases ◽

Heme Oxygenase ◽

Therapeutic Potential ◽

Redox Homeostasis ◽

Antioxidant Defenses ◽

Heme Oxygenase 1 ◽

Physiological Conditions ◽

And Oxidative Stress ◽

Defensive Mechanism

Heme oxygenase (HO) family catalyzes the conversion of heme into free iron, carbon monoxide and biliverdin. It possesses two well-characterized isoforms: HO-1 and HO-2. Under brain physiological conditions, the expression of HO-2 is constitutive, abundant and ubiquitous, whereas HO-1 mRNA and protein are restricted to small populations of neurons and neuroglia. HO-1 is an inducible enzyme that has been shown to participate as an essential defensive mechanism for neurons exposed to oxidant challenges, being related to antioxidant defenses in certain neuropathological conditions. Considering that neurodegenerative diseases (Alzheimer’s Disease (AD), Parkinson’s Disease (PD) and Multiple Sclerosis (MS)) and neuropsychiatric disorders (depression, anxiety, Bipolar Disorder (BD) and schizophrenia) are associated with increased inflammatory markers, impaired redox homeostasis and oxidative stress, conditions that may be associated with alterations in HO-levels/activity, the purpose of this review is to present evidence on the possible role of HO-1 in these Central Nervous System (CNS) diseases. In addition, the possible therapeutic potential of targeting brain HO-1 is explored in this review.

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Exploring the Role of Aggregated Proteomes in the Pathogenesis of Alzheimer’s Disease

Current Protein and Peptide Science ◽

10.2174/1389203721666200921152246 ◽

2020 ◽

Vol 21 (12) ◽

pp. 1164-1173

Author(s):

Siju Ellickal Narayanan ◽

Nikhila Sekhar ◽

Rajalakshmi Ganesan Rajamma ◽

Akash Marathakam ◽

Abdullah Al Mamun ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Precursor Protein ◽

Early Onset ◽

Late Onset ◽

Precursor Protein ◽

Brain Disorder ◽

Amyloid Aβ ◽

T Tau

: Alzheimer’s disease (AD) is a progressive brain disorder and one of the most common causes of dementia and death. AD can be of two types; early-onset and late-onset, where late-onset AD occurs sporadically while early-onset AD results from a mutation in any of the three genes that include amyloid precursor protein (APP), presenilin 1 (PSEN 1) and presenilin 2 (PSEN 2). Biologically, AD is defined by the presence of the distinct neuropathological profile that consists of the extracellular β-amyloid (Aβ) deposition in the form of diffuse neuritic plaques, intraneuronal neurofibrillary tangles (NFTs) and neuropil threads; in dystrophic neuritis, consisting of aggregated hyperphosphorylated tau protein. Elevated levels of (Aβ), total tau (t-tau) and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) have become an important biomarker for the identification of this neurodegenerative disease. The aggregation of Aβ peptide derived from amyloid precursor protein initiates a series of events that involve inflammation, tau hyperphosphorylation and its deposition, in addition to synaptic dysfunction and neurodegeneration, ultimately resulting in dementia. The current review focuses on the role of proteomes in the pathogenesis of AD.

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