scholarly journals Pathology dynamics in healthy-toxic protein interaction and the multiscale analysis of neurodegenerative diseases

2021 ◽  
Author(s):  
Swadesh Pal ◽  
Roderick Melnik
Keyword(s):  
Neurodegenerative Diseases ◽  
Protein Interaction ◽  
Tau Protein ◽  
Multiscale Analysis ◽  
Reaction Diffusion ◽  
Modified Model ◽  
Toxic Protein ◽  
Conversion Time ◽  
Critical Characteristics ◽  
Toxic Proteins

Neurodegenerative diseases are frequently associated with aggregation and propagation of toxic proteins. In particular, it is well known that along with amyloid-beta, the tau protein is also driving Alzheimer's disease. Multiscale reaction-diffusion models can assist in our better understanding of the evolution of the disease. We have modified the heterodimer model in such a way that it can now capture some of critical characteristics of this evolution such as the conversion time from healthy to toxic proteins. We have analyzed the modified model theoretically and validated the theoretical findings with numerical simulations.

scholarly journals Mechanisms of Neurodegeneration in Various Forms of Parkinsonism—Similarities and Differences

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 656
Author(s):  
Dariusz Koziorowski ◽  
Monika Figura ◽  
Łukasz M. Milanowski ◽  
Stanisław Szlufik ◽  
Piotr Alster ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Tau Protein ◽  
Protein Gene ◽  
Clinical Presentation ◽  
Neuronal Loss ◽  
Corticobasal Degeneration ◽  
Inflammatory Factors ◽  
Parkinsonian Disorders ◽  
Genetic Features ◽  
The Brain

Parkinson's disease (PD), dementia with Lewy body (DLB), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA) belong to a group of neurodegenerative diseases called parkinsonian syndromes. They share several clinical, neuropathological and genetic features. Neurodegenerative diseases are characterized by the progressive dysfunction of specific populations of neurons, determining clinical presentation. Neuronal loss is associated with extra- and intracellular accumulation of misfolded proteins. The parkinsonian diseases affect distinct areas of the brain. PD and MSA belong to a group of synucleinopathies that are characterized by the presence of fibrillary aggregates of α-synuclein protein in the cytoplasm of selected populations of neurons and glial cells. PSP is a tauopathy associated with the pathological aggregation of the microtubule associated tau protein. Although PD is common in the world's aging population and has been extensively studied, the exact mechanisms of the neurodegeneration are still not fully understood. Growing evidence indicates that parkinsonian disorders to some extent share a genetic background, with two key components identified so far: the microtubule associated tau protein gene (MAPT) and the α-synuclein gene (SNCA). The main pathways of parkinsonian neurodegeneration described in the literature are the protein and mitochondrial pathways. The factors that lead to neurodegeneration are primarily environmental toxins, inflammatory factors, oxidative stress and traumatic brain injury.

Heparin remodels the microtubule-binding repeat R3 of Tau protein towards fibril-prone conformations

2021 ◽  
Author(s):  
Xuewei Dong ◽  
Ruxi Qi ◽  
Qin Qiao ◽  
Xuhua Li ◽  
Fangying Li ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Tau Protein ◽  
Amyloid Fibrils ◽  
Microtubule Binding ◽  
Wide Range

Abnormal aggregation of proteins into pathological amyloid fibrils are implicated in a wide range of devastating human neurodegenerative diseases. Intracellular fibrillary inclusions formed by Tau protein are characterized as the...

26. The pathobiology of tau protein in neurodegenerative diseases

2000 ◽  
Vol 47 (8) ◽  
pp. S7
Author(s):  
R.A. Nixon ◽  
K. Duff ◽  
Y. Matsuoka
Keyword(s):  
Neurodegenerative Diseases ◽  
Tau Protein

scholarly journals From genetics to pathology: tau and a–synuclein assemblies in neurodegenerative diseases

2001 ◽  
Vol 356 (1406) ◽  
pp. 213-227 ◽  
Author(s):  
Michel Goedert ◽  
Maria Grazia Spillantini ◽  
Louise C. Serpell ◽  
John Berriman ◽  
Michael J. Smith ◽  
...  
Keyword(s):  
Human Brain ◽  
Neurodegenerative Diseases ◽  
Frontotemporal Dementia ◽  
Glial Cells ◽  
Tau Protein ◽  
Nerve Cells ◽  
Degenerative Diseases ◽  
Protein Tau ◽  
Microtubule Associated Protein Tau ◽  
Filamentous Inclusions

The most common degenerative diseases of the human brain are characterized by the presence of abnormal filamentous inclusions in affected nerve cells and glial cells. These diseases can be grouped into two classes, based on the identity of the major proteinaceous components of the filamentous assemblies. The filaments are made of either the microtubule–associated protein tau or the protein α–synuclein. Importantly, the discovery of mutations in the tau gene in familial forms of frontotemporal dementia and of mutations in the α–synuclein gene in familial forms of Parkinson's disease has established that dysfunction of tau protein and α–synuclein can cause neurodegeneration.

scholarly journals An immuno-enrichment free, validated quantification of tau protein in human CSF by LC-MS/MS

2021 ◽  
Author(s):  
Wade Self ◽  
John P. Savaryn ◽  
Khader Awwad ◽  
Michael Schulz
Keyword(s):  
Cerebrospinal Fluid ◽  
Neurodegenerative Diseases ◽  
Tau Protein ◽  
Therapeutic Antibodies ◽  
Alzheimers Disease ◽  
Total Tau ◽  
Human Cerebrospinal Fluid ◽  
Fit For Purpose

Aims: Tau protein is a key target of interest in developing therapeutics for neurodegenerative diseases. Here, we sought to develop a method that quantifies extracellular tau protein concentrations human cerebrospinal fluid (CSF) without antibody-based enrichment strategies. Results: We demonstrate that the fit-for-purpose validated method in Alzheimers Disease CSF is limited to quasi quantitative measures of tau surrogate peptides. We also provide evidence that CSF total Tau measures by LC-MS are feasible in the presence of monoclonal therapeutic antibodies in human CSF. Conclusion: Our Tau LC-MS/MS method is a translational bioanalytical tool for assaying target

scholarly journals Front propagation and arrival times in networks with application to neurodegenerative diseases

2022 ◽  
Author(s):  
Prama Setia Putra ◽  
Hadrien Oliveri ◽  
Travis B Thompson ◽  
Alain Goriely
Keyword(s):  
Neurodegenerative Diseases ◽  
Arrival Time ◽  
Initial Conditions ◽  
Front Propagation ◽  
Small Concentration ◽  
Single Node ◽  
Arrival Times ◽  
Toxic Protein ◽  
Time Estimates ◽  
Analytical Complexity

Many physical, epidemiological, or physiological dynamical processes on networks support front-like propagation, where an initial localized perturbation grows and systematically invades all nodes in the network. A key question is then to extract estimates for the dynamics. In particular, if a single node is seeded at a small concentration, when will other nodes reach the same initial concentration? Here, motivated by the study of toxic protein propagation in neurodegenerative diseases, we present and compare three different estimates for the arrival time in order of increasing analytical complexity: the linear arrival time, obtained by linearizing the underlying system; the Lambert time, obtained by considering the interaction of two nodes; and the nonlinear arrival time, obtained by asymptotic techniques. We use the classic Fisher-Kolmogorov-Petrovsky-Piskunov equation as a paradigm for the dynamics and show that each method provides different insight and time estimates. Further, we show that the nonlinear asymptotic method also gives an approximate solution valid in the entire domain and the correct ordering of arrival regions over large regions of parameters and initial conditions.

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