Tau Abnormalities and Autophagic Defects in Neurodegenerative Disorders; A Feed-forward Cycle

Samimi, Nastaran; Asada, Akiko; Ando, Kanae

doi:10.31661/gmj.v9i0.1681

Cited by 3 publications

(3 citation statements)

References 76 publications

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“…Two major mechanisms that degrade the abnormal protein in cells are ubiquitinproteasome system (UPS) and autophagy lysosomal pathway (ALP) [96,97]. Alterations of these proteolytic systems result in tau accumulation and often accompany pathological conditions [98,99].…”

Section: Clearance Of Misfolded Tau By Protein Degradation Systemmentioning

confidence: 99%

Modulation of Tau Pathology in Alzheimer’s Disease by Dietary Bioactive Compounds

Shi,

Zhao

2024

IJMS

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Tau is a microtubule-associated protein essential for microtubule assembly and stability in neurons. The abnormal intracellular accumulation of tau aggregates is a major characteristic of brains from patients with Alzheimer’s disease (AD) and other tauopathies. In AD, the presence of neurofibrillary tangles (NFTs), which is composed of hyperphosphorylated tau protein, is positively correlated with the severity of the cognitive decline. Evidence suggests that the accumulation and aggregation of tau cause synaptic dysfunction and neuronal degeneration. Thus, the prevention of abnormal tau phosphorylation and elimination of tau aggregates have been proposed as therapeutic strategies for AD. However, currently tau-targeting therapies for AD and other tauopathies are limited. A number of dietary bioactive compounds have been found to modulate the posttranslational modifications of tau, including phosphorylation, small ubiquitin-like modifier (SUMO) mediated modification (SUMOylation) and acetylation, as well as inhibit tau aggregation and/or promote tau degradation. The advantages of using these dietary components over synthetic substances in AD prevention and intervention are their safety and accessibility. This review summarizes the mechanisms leading to tau pathology in AD and highlights the effects of bioactive compounds on the hyperphosphorylation, aggregation and clearance of tau protein. The potential of using these bioactive compounds for AD prevention and intervention is also discussed.

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Section: Clearance Of Misfolded Tau By Protein Degradation Systemmentioning

confidence: 99%

Modulation of Tau Pathology in Alzheimer’s Disease by Dietary Bioactive Compounds

Shi,

Zhao

2024

IJMS

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“…This is a valuable finding because the autophagic pathway is essential for the degradation of pathological MAPT/tau as well as intracellular infectious pathogens. Autophagic dysfunction caused by or resulting from MAPT/tau hyperphosphorylation received a great deal of attention in recent years [ 36 , 37 ]. Further investigations are necessary to evaluate the COVID-19-associated MAPT/tau pathology and autophagy dysfunction in the brain.…”

Section: The Role Of Autophagy In Sars-cov-2-infected Glial and Neural Cellsmentioning

confidence: 99%

The role of autophagy in the pathogenesis of SARS-CoV-2 infection in different cell types

2021

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“…Ehrlich and colleagues further demonstrated activation of unfolded protein response in FTDP-17 neurons as well as FTDP-17-associated gene expression profiles. Furthermore, research has uncovered a link between TAU mutations and defects in organelle trafficking, which is essential for proper cellular function [ 34 , 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

MAPT Mutations V337M and N297K Alter Organelle Trafficking in Frontotemporal Dementia Patient-Specific Motor Neurons

Hartmann,

Anskat,

Ehrlich

et al. 2024

Biomedicines

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Frontotemporal dementia (FTD) is a neurodegenerative disease characterized by the progressive loss of neurons mainly in the frontal and temporal lobes of the brain. Mutations (e.g., V337M, N297K) in the microtubule-associated protein TAU (MAPT) are responsible 5–20% of familial FTD cases and have been associated with defects in organelle trafficking that plays a critical role in the proper function of cells, including transport of essential molecules and degradation of waste products. Due to the critical role of TAU mutations in microtubule stabilization and organelle transportation, it is of great interest to study these molecular mechanisms to develop effective therapeutic strategies. Therefore, herein, we analyzed mitochondrial and lysosomal trafficking in disease-specific spinal motor neurons by using live cell imaging in undirected (uncompartmentalized) and directed (compartmentalized) cell culture systems. While V337M neurons only expressed 3R TAU, the N297K mutant neurons expressed both 3R and 4R TAU. Axonal trafficking was affected differentially in V337M and N297 MAPT mutated neurons. These findings suggest that the MAPT mutations V337M and N297K impaired axon physiology differentially, which highlights the need for mutation- and/or 3R/4R TAU-specific therapeutic approaches.

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Tau Abnormalities and Autophagic Defects in Neurodegenerative Disorders; A Feed-forward Cycle

Cited by 3 publications

References 76 publications

Modulation of Tau Pathology in Alzheimer’s Disease by Dietary Bioactive Compounds

Modulation of Tau Pathology in Alzheimer’s Disease by Dietary Bioactive Compounds

The role of autophagy in the pathogenesis of SARS-CoV-2 infection in different cell types

MAPT Mutations V337M and N297K Alter Organelle Trafficking in Frontotemporal Dementia Patient-Specific Motor Neurons

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