Improved behavioral response as a valid biomarker for drug screening program in transgenic rodent models of tauopathies.

Cell Mol Neurobiol

Institute of Neuroimmunology, Slovak Academy of Sciences, AD Centre, Bratislava 845 10, Slovak Republic.

Published: September 2009

AI Article Synopsis

  • Neurodegenerative tauopathies are a group of disorders characterized by abnormal tau protein aggregates in the brain, leading to dementia and movement issues.
  • Transgenic model organisms have been developed to study the specific pathways and potential therapies related to tau-related neurodegenerative diseases.
  • Two main types of behavioral impairments in these models include progressive motor impairment and cognitive decline, yet only motor impairment models have been effective in drug trials, highlighting a gap between these models and human conditions.

Article Abstract

Neurodegenerative tauopathies are defined as a group of dementia and movement disorders characterized by prominent filamentous tau inclusions and degeneration located within certain brain regions. Their common sign is a presence of proteinaceous aggregates composed of hyperphosphorylated and truncated tau proteins. The molecular mechanisms of the disease still remain unresolved, therefore transgenic organisms displaying tau-related neurodegenerative cascade have been created to allow decoding of individual pathways involved in human pathological conditions. Moreover, use of transgenic model organisms enables the application of potential therapeutic approaches. The expression of mutated or misfolded tau as a transgene in vivo leads to significant alteration of neurobehavioral features of experimental animal, therefore detailed classification of behavioral phenotype become one of the first crucial analyses, while it functionally correlates with central nervous system impairment. Currently, two major types of behavioral impairment have been described in transgenic rodent models of tauopathies, (1) progressive motor impairment associated with muscular weakness and premature death and (2) age-related impairment of cognitive functions attended with unaffected motor status. Up to the present, only transgenic models displaying motor impairment were successfully applied into the drug trials targeting misfolded tau protein, despite their behavioral inconsistence with clinical profile of progressive human tauopathy. The aim of this study was, therefore, to summarize the pros and cons of used transgenic rodent models mimicking human tauopathies in connection with development of therapeutic strategies.

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http://dx.doi.org/10.1007/s10571-009-9378-2DOI Listing

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