scholarly journals Uncoupling protein 4 (UCP4) gene variability in neurodegenerative disorders: further evidence of association in Frontotemporal dementia

Aging ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 3283-3293 ◽  
Author(s):  
Alberto Montesanto ◽  
Paolina Crocco ◽  
Serena Dato ◽  
Silvana Geracitano ◽  
Francesca Frangipane ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Neurodegenerative Disorders ◽  
Uncoupling Protein ◽  
Uncoupling Protein 4 ◽  
Gene Variability

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.

scholarly journals Differential compartmental processing and phosphorylation of pathogenic human tau and native mouse tau in the line 66 model of frontotemporal dementia

2020 ◽  
Vol 295 (52) ◽  
pp. 18508-18523
Author(s):  
Nora Lemke ◽  
Valeria Melis ◽  
Dilyara Lauer ◽  
Mandy Magbagbeolu ◽  
Boris Neumann ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Tau Protein ◽  
Neurodegenerative Disorders ◽  
Genetic Variants ◽  
Subcellular Fractionation ◽  
Brain Regions ◽  
Transgenic Mouse Model ◽  
Protein Species ◽  
Synapse Loss ◽  
Triton X

Synapse loss is associated with motor and cognitive decline in multiple neurodegenerative disorders, and the cellular redistribution of tau is related to synaptic impairment in tauopathies, such as Alzheimer's disease and frontotemporal dementia. Here, we examined the cellular distribution of tau protein species in human tau overexpressing line 66 mice, a transgenic mouse model akin to genetic variants of frontotemporal dementia. Line 66 mice express intracellular tau aggregates in multiple brain regions and exhibit sensorimotor and motor learning deficiencies. Using a series of anti-tau antibodies, we observed, histologically, that nonphosphorylated transgenic human tau is enriched in synapses, whereas phosphorylated tau accumulates predominantly in cell bodies and axons. Subcellular fractionation confirmed that human tau is highly enriched in insoluble cytosolic and synaptosomal fractions, whereas endogenous mouse tau is virtually absent from synapses. Cytosolic tau was resistant to solubilization with urea and Triton X-100, indicating the formation of larger tau aggregates. By contrast, synaptic tau was partially soluble after Triton X-100 treatment and most likely represents aggregates of smaller size. MS corroborated that synaptosomal tau is nonphosphorylated. Tau enriched in the synapse of line 66 mice, therefore, appears to be in an oligomeric and nonphosphorylated state, and one that could have a direct impact on cognitive function.

scholarly journals Control of Mitochondrial pH by Uncoupling Protein 4 in Astrocytes Promotes Neuronal Survival

2014 ◽  
Vol 289 (45) ◽  
pp. 31014-31028 ◽  
Author(s):  
Hélène Perreten Lambert ◽  
Manuel Zenger ◽  
Guillaume Azarias ◽  
Jean-Yves Chatton ◽  
Pierre J. Magistretti ◽  
...  
Keyword(s):  
Neuronal Survival ◽  
Uncoupling Protein ◽  
Uncoupling Protein 4
Sign in / Sign up

Export Citation Format

Share Document