Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
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Query: UNIPROT:P10636 (
tau protein
)
5,110
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Mutations in the gene encoding Tau (
MAPT
-
microtubule-associated protein tau
) cause a group of neurodegenerative diseases called tauopathies. A recently identified Tau variant, p.A152T, has been reported as a risk factor for frontotemporal dementia-related disorders and Alzheimer disease. However, the mechanism for the pathologies still remain poorly understood. Transgenic Caenorhabditis elegans expressing mutant 2N4R-Tau
A152T
(Tau
AT
) panneuronally show locomotor defects, neurodegeneration and accelerated aging. Here we report that, in Tau
AT
animals, the glutamatergic nervous system is at a high risk of progressive neuronal loss. We present genetic data that this loss occurs predominantly through necrosis. The neuronal loss is caused by several determinants, such as altered adenylyl cyclase (type
AC9
) pathway, prevalence of excitotoxicity-like conditions, aging-related factors and finally dyshomeostasis of intracellular calcium (Ca
2+
). The study provides novel insights into the mechanisms involved in selective loss of glutamatergic neurons in a Tau
AT
tauopathy model which could point to new therapeutic targets.
...
PMID:Glutamatergic nervous system degeneration in a C. elegans Tau
A152T
tauopathy model involves pathways of excitotoxicity and Ca
2+
dysregulation. 2989 52
