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...

Structure, Function and Interactions of Tau: Particular Focus on Potential Drug Targets for the Treatment of Tauopathies

2018 ◽  
Vol 17 (5) ◽  
pp. 325-337 ◽  
Author(s):  
Hojjat Borna ◽  
Kasim Assadoulahei ◽  
Gholamhossein Riazi ◽  
Asghar Beigi Harchegani ◽  
Alireza Shahriary
Keyword(s):  
Tau Protein ◽  
Drug Targets ◽  
Brain Injuries ◽  
Potential Drug ◽  
Microtubule Network ◽  
Wide Range ◽  
Potential Risk Factors ◽  
Range Of Functions ◽  
Potential Drug Targets

Background & Objective: Neurodegenrative diseases are among the most widespread lifethreatening disorders around the world in elderly ages. The common feature of a group of neurodegenerative disorders, called tauopathies, is an accumulation of microtubule associated protein tau inside the neurons. The exact mechanism underlying tauopathies is not well-understood but several factors such as traumatic brain injuries and genetics are considered as potential risk factors. Although tau protein is well-known for its key role in stabilizing and organization of axonal microtubule network, it bears a broad range of functions including DNA protection and participation in signaling pathways. Moreover, the flexible unfolded structure of tau facilitates modification of tau by a wide range of intracellular enzymes which in turn broadens tau function and interaction spectrum. The distinctive properties of tau protein concomitant with the crucial role of tau interaction partners in the progression of neurodegeneration suggest tau and its binding partners as potential drug targets for the treatment of neurodegenerative diseases. Conclusion: This review aims to give a detailed description of structure, functions and interactions of tau protein in order to provide insight into potential therapeutic targets for treatment of tauopathies.

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.

scholarly journals Zebrafish Models to Study New Pathways in Tauopathies

2021 ◽  
Vol 22 (9) ◽  
pp. 4626
Author(s):  
Clément Barbereau ◽  
Nicolas Cubedo ◽  
Tangui Maurice ◽  
Mireille Rossel
Keyword(s):  
Cognitive Deficits ◽  
Tau Protein ◽  
Common Point ◽  
Transgenic Models ◽  
Synaptic Loss ◽  
Wide Range ◽  
Transgenic Lines ◽  
Functional Consequences ◽  
The Common

Tauopathies represent a vast family of neurodegenerative diseases, the most well-known of which is Alzheimer’s disease. The symptoms observed in patients include cognitive deficits and locomotor problems and can lead ultimately to dementia. The common point found in all these pathologies is the accumulation in neural and/or glial cells of abnormal forms of Tau protein, leading to its aggregation and neurofibrillary tangles. Zebrafish transgenic models have been generated with different overexpression strategies of human Tau protein. These transgenic lines have made it possible to highlight Tau interacting factors or factors which may limit the neurotoxicity induced by mutations and hyperphosphorylation of the Tau protein in neurons. Several studies have tested neuroprotective pharmacological approaches. On few-days-old larvae, modulation of various signaling or degradation pathways reversed the deleterious effects of Tau mutations, mainly hTauP301L and hTauA152T. Live imaging and live tracking techniques as well as behavioral follow-up enable the analysis of the wide range of Tau-related phenotypes from synaptic loss to cognitive functional consequences.

scholarly journals Polarity-active NIR probes with strong two-photon absorption and ultrahigh binding affinity of insulin amyloid fibrils

2021 ◽  
Author(s):  
Li Li ◽  
Zheng Lv ◽  
Zhongwei Man ◽  
Zhenzhen Xu ◽  
YuLing Wei ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Binding Affinity ◽  
Fluorescent Probes ◽  
Amyloid Fibrils ◽  
Photon Absorption ◽  
Two Photon Absorption ◽  
Two Photon ◽  
Medical Diagnostic

Amyloid fibrils are associated with many neurodegenerative diseases. In-situ and in-vivo visualization of amyloid fibrils is important for medical diagnostic and requires fluorescent probes with both excitation and emission wavelengths in...

scholarly journals Axotrophin/MARCH7 acts as an E3 ubiquitin ligase and ubiquitinates tau protein in vitro impairing microtubule binding

2014 ◽  
Vol 1842 (9) ◽  
pp. 1527-1538 ◽  
Author(s):  
Katharina Flach ◽  
Ellen Ramminger ◽  
Isabel Hilbrich ◽  
Annika Arsalan-Werner ◽  
Franziska Albrecht ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Tau Protein ◽  
E3 Ubiquitin Ligase ◽  
Microtubule Binding

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

Phosphorylation, Microtubule Binding and Aggregation of Tau Protein in Alzheimer's Disease

2003 ◽  
pp. 601-607
Author(s):  
Jesús Ávila ◽  
José J. Lucas ◽  
Filip Lim ◽  
Mar Pérez ◽  
Félix Hernández ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Microtubule Binding

Smuggle tau through a secret(ory) pathway

2021 ◽  
Vol 478 (14) ◽  
pp. 2921-2925
Author(s):  
Hao Xu (徐昊)
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Recent Work ◽  
Molecular Mechanisms ◽  
Binding Protein ◽  
Nerve Cells ◽  
Transmembrane Domains ◽  
Tau Pathology ◽  
Microtubule Binding

Secretion of misfolded tau, a microtubule-binding protein enriched in nerve cells, is linked to the progression of tau pathology. However, the molecular mechanisms underlying tau secretion are poorly understood. Recent work by Lee et al. [Biochemical J. (2021) 478: 1471–1484] demonstrated that the transmembrane domains of syntaxin6 and syntaxin8 could be exploited for tau release, setting a stage for testing a novel hypothesis that has profound implications in tauopathies (e.g. Alzheimer's disease, FTDP-17, and CBD/PSP) and other related neurodegenerative diseases. The present commentary highlights the importance and limitations of the study, and discusses opportunities and directions for future investigations.

Super Nutritive Marine Astaxanthin, an Effectual Dietary Carotenoid for Neurodegenerative Diseases

2019 ◽  
pp. 115-124 ◽  
Author(s):  
Kumaresan Kowsalya ◽  
Nandakumar Vidya ◽  
Vijayraj Vijayalakshmi ◽  
Muthukrishnan Arun
Keyword(s):  
Neurodegenerative Diseases ◽  
Cell Membranes ◽  
Uv Light ◽  
Coenzyme Q ◽  
Skin Pigmentation ◽  
Beta Carotene ◽  
Wide Range ◽  
Commercial Applications ◽  
Dietary Carotenoid ◽  
Single Oxygen

The red-pigmented astaxanthin (3,-3’-dihydroxy-?,?-carotene-4,4’-dione) were commonly found in marine algae and aquatic animals such as shrimp, lobster, and trout. These pigments are produced as secondary metabolites which fall in arytenoids under class xanthophylls. Synthetic astaxanthin has a wide range of commercial applications such as color additives, usage in cosmetics and immune-boosters. In aquaculture, supplementing synthetic astaxanthin as feed, enhances skin pigmentation which possesses commercial importance. However, synthetic astaxanthin is not highly efficient compared to naturally derived counter forms. On the other hand, humans should only depend on microbial and aquatic sources for their dietary intake of natural astaxanthin. Being a powerful antioxidant, natural astaxanthin is called as king of antioxidants which has scavenging activity 6000 times stronger than vitamin C and 50 times more powerful than vitamin E in protecting cell membranes. It also has a single oxygen quenching activity up to 800 times stronger than coenzyme Q, 550 times more powerful than green tea catechins, 4.9 times stronger than beta-carotene and three times stronger than lute in. Furthermore, researchers revealed that this carotenoid has the capacity to alleviate tumor activity, protecting against lipid per oxidation, free radicals, oxidative damage to LDL-cholesterol and UV light affects on cell membranes and tissues. Also, it is mainly recommended for curing the macular degeneration of cataracts. Anti-aging properties of astaxanthin improve skin health by reducing wrinkles and repairs the UV-induced DNA damage in human cells. Interestingly, the ability of astaxanthin in crossing the blood-brain barrier has brought this compound to limelight as a potential target in treating neurodegenerative diseases including Parkinson's and Alzheimer's disease. Hence, in this review, we are mainly focusing on the therapeutic usage of astaxanthin in neurodegenerative diseases.

Conformational transition state is responsible for assembly of microtubule-binding domain of tau protein

2004 ◽  
Vol 315 (3) ◽  
pp. 659-663 ◽  
Author(s):  
Shuko Hiraoka ◽  
Tian-Ming Yao ◽  
Katsuhiko Minoura ◽  
Koji Tomoo ◽  
Miho Sumida ◽  
...  
Keyword(s):  
Transition State ◽  
Tau Protein ◽  
Conformational Transition ◽  
Binding Domain ◽  
Microtubule Binding ◽  
Microtubule Binding Domain
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