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Cell-mediated neuroprotection in a mouse model of human tauopathy.

TitleCell-mediated neuroprotection in a mouse model of human tauopathy.
Publication TypeJournal Article
Year of Publication2010
AuthorsHampton DW, Webber DJ, Bilican B, Goedert M, Spillantini MGrazia, Chandran S
JournalJ Neurosci
Date Published2010 Jul 28
KeywordsAge Factors, Animals, Basic Helix-Loop-Helix Transcription Factors, Cell Differentiation, Cell Transplantation, Cell- and Tissue-Based Therapy, Cells, Cultured, Cerebral Cortex, Disease Models, Animal, Female, gamma-Aminobutyric Acid, Gene Expression Regulation, Glial Cell Line-Derived Neurotrophic Factor, Green Fluorescent Proteins, Homeodomain Proteins, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Nerve Growth Factor, Nerve Tissue Proteins, Neurons, Proline, RNA, Messenger, Serine, Stem Cells, tau Proteins, Tauopathies

Tau protein in a hyperphosphorylated state makes up the intracellular inclusions of several neurodegenerative diseases, including Alzheimer's disease and cases of frontotemporal dementia. Mutations in Tau cause familial forms of frontotemporal dementia, establishing that dysfunction of tau protein is sufficient to cause neurodegeneration and dementia. Transgenic mice expressing human mutant tau in neurons exhibit the essential features of tauopathies, including neurodegeneration and abundant filaments composed of hyperphosphorylated tau. Here we show that a previously described mouse line transgenic for human P301S tau exhibits an age-related, layer-specific loss of superficial cortical neurons, similar to what has been observed in human frontotemporal dementias. We also show that focal neural precursor cell implantation, resulting in glial cell differentiation, leads to the sustained rescue of cortical neurons. Together with evidence indicating that astrocyte transplantation may be neuroprotective, our findings suggest a beneficial role for glial cell-based repair in neurodegenerative diseases.

Alternate JournalJ. Neurosci.
PubMed ID20668182
Grant ListMC_U105184291 / / Medical Research Council / United Kingdom
/ / Medical Research Council / United Kingdom