ABSTRACT
Intracellular assembly of microtubule-associated protein tau into filamentous inclusions is central to Alzheimer's disease and related disorders collectively known as tauopathies. Although tau mutations, posttranslational modifications and degradations have been the focus of investigations, the mechanism of tau fibrillogenesis in vivo still remains elusive. Different strategies have been undertaken to generate animal and cellular models for tauopathies. Some are used to study the molecular events leading to the assembly and accumulation of tau filaments, and others to identify potential therapeutic agents that are capable of impeding tauopathy. This review highlights the latest developments in new models and how their utility improves our understanding of the sequence of events leading to human tauopathy.
Subject(s)
Tauopathies/etiology , tau Proteins/physiology , Animals , Cells, Cultured , Disease Models, Animal , Humans , Mice , Mice, Transgenic , Mutation , Neurofibrils/physiology , Protein Isoforms/metabolism , Protein Processing, Post-Translational , Tauopathies/drug therapy , Transfection , tau Proteins/geneticsABSTRACT
Filamentous inclusions made of phosphorylated tau constitute a neuropathologic hallmark of Alzheimer's disease and related disorders. Because abnormal accumulation of tau correlates with the decline in cognitive function, it is conceivable that effective intervention at the early stage of tau filament assembly could impede the progression of these neurodegnerative diseases. Cellular models recapitulating the tau aberration are useful for screening and identifying compounds that are capable of interfering with tau aggregation in a cost-effective manner. To develop such cell culture models, we have established from human neuroglioma [H4] and neuronal [BE(2)-M17D] cells conditional transfectants whose transgenic expression of wild-type or mutant tau via inducible expression mechanisms leads to tau aggregation and filament assembly.
