scholarly journals DrosophilaModels of Tauopathies: What Have We Learned?

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Marc Gistelinck ◽  
Jean-Charles Lambert ◽  
Patrick Callaerts ◽  
Bart Dermaut ◽  
Pierre Dourlen
Keyword(s):  
Frontotemporal Dementia ◽  
High Throughput ◽  
Neurodegenerative Disorders ◽  
Genetic Model ◽  
Model Organism ◽  
Molecular Pathways ◽  
Protein Tau ◽  
Microtubule Associated Protein Tau ◽  
The Past ◽  
Genome Wide

Aggregates of the microtubule-associated protein Tau are neuropathological hallmark lesions in Alzheimer's disease (AD) and related primary tauopathies. In addition, Tau is genetically implicated in a number of human neurodegenerative disorders including frontotemporal dementia (FTD) and Parkinson's disease (PD). The exact mechanism by which Tau exerts its neurotoxicity is incompletely understood. Here, we give an overview of how studies using the genetic model organismDrosophilaover the past decade have contributed to the molecular understanding of Tau neurotoxicity. We compare the different available readouts for Tau neurotoxicity in flies and review the molecular pathways in which Tau has been implicated. Finally, we emphasize that the integration of genome-wide approaches in human or mice with high-throughput genetic validation inDrosophilais a fruitful approach.

Shaping the nebulous enhancer in the era of high-throughput assays and genome editing

2019 ◽  
Vol 21 (3) ◽  
pp. 836-850
Author(s):  
Edwin Yu-Kiu Ho ◽  
Qin Cao ◽  
Mengting Gu ◽  
Ricky Wai-Lun Chan ◽  
Qiong Wu ◽  
...  
Keyword(s):  
Genome Editing ◽  
High Throughput ◽  
Wide Spectrum ◽  
Data Interpretation ◽  
Future Studies ◽  
Transcriptional Enhancers ◽  
The Past ◽  
Genome Wide ◽  
Gray Areas ◽  
Practical Implications

Abstract Since the 1st discovery of transcriptional enhancers in 1981, their textbook definition has remained largely unchanged in the past 37 years. With the emergence of high-throughput assays and genome editing, which are switching the paradigm from bottom-up discovery and testing of individual enhancers to top-down profiling of enhancer activities genome-wide, it has become increasingly evidenced that this classical definition has left substantial gray areas in different aspects. Here we survey a representative set of recent research articles and report the definitions of enhancers they have adopted. The results reveal that a wide spectrum of definitions is used usually without the definition stated explicitly, which could lead to difficulties in data interpretation and downstream analyses. Based on these findings, we discuss the practical implications and suggestions for future studies.

scholarly journals Invited review: Frontotemporal dementia caused by microtubule‐associated protein tau gene ( MAPT ) mutations: a chameleon for neuropathology and neuroimaging

2015 ◽  
Vol 41 (1) ◽  
pp. 24-46 ◽  
Author(s):  
Bernardino Ghetti ◽  
Adrian L. Oblak ◽  
Bradley F. Boeve ◽  
Keith A. Johnson ◽  
Bradford C. Dickerson ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Protein Tau ◽  
Microtubule Associated Protein Tau

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

2020 ◽  
Vol 9 ◽  
pp. 1681
Author(s):  
Nastaran Samimi ◽  
Akiko Asada ◽  
Kanae Ando
Keyword(s):  
Neurodegenerative Disorders ◽  
Short Review ◽  
Misfolded Proteins ◽  
Protein Accumulation ◽  
Disease Pathogenesis ◽  
Feed Forward ◽  
Abnormal Protein ◽  
Protein Tau ◽  
Microtubule Associated Protein Tau ◽  
The Relationship

Abnormal deposition of misfolded proteins is a neuropathological characteristic shared by many neurodegenerative disorders including Alzheimer’s disease (AD). Generation of excessive amounts of aggregated proteins and impairment of degradation systems for misfolded proteins such as autophagy can lead to accumulation of proteins in diseased neurons. Molecules that contribute to both these effects are emerging as critical players in disease pathogenesis. Furthermore, impairment of autophagy under disease conditions can be both a cause and a consequence of abnormal protein accumulation. Specifically, disease-causing proteins can impair autophagy, which further enhances the accumulation of abnormal proteins. In this short review, we focus on the relationship between the microtubule-associated protein tau and autophagy to highlight a feed-forward mechanism in disease pathogenesis. [GMJ.2020;9:e1681]

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