Misfolded tau protein and disease modifying pathways in transgenic rodent models of human tauopathies.
Human tauopathies represent a heterogeneous group of neurodegenerative disorders such as Alzheimer's disease (AD) that are characterized by the presence of intracellular accumulations of abnormal filaments of protein tau. Presently, AD poses an increasing public health concern, because it affects nearly 2% of the population in industrialized countries and the number of patients is expected to increase threefold within the next 50 years. Therefore, the identification of disease modifying pathways that will lead to the development of novel therapeutic approaches targeting downstream molecular events of the tauopathy is of paramount importance. In order to identify factors that may exacerbate or inhibit the disease phenotype a number of genetically modified rodent models reproducing key clinical, histopathological and molecular hallmarks of human tauopathies were developed. Current tau transgenic rodent models express as a transgene either an individual or all six human wild-type tau isoforms, mutant tau linked to FTDP-17, or structurally modified tau species derived from AD. In this review we will provide an up-to-date account of various facets of the tau neurodegenerative cascade with a special emphasis on the evolution of neurofibrillary tangles, neuronal death and neuroinflammation.
Zilka
Norbert
N
Centre of Excellence for Alzheimer's Disease and Related Disorders, Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska 9, 84510 Bratislava, Slovak Republic.
Korenova
Miroslava
M
Novak
Michal
M
D000818:Animals; D030801:Animals, Genetically Modified; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D009410:Nerve Degeneration; D009474:Neurons / Q000473:pathology / Q000502:physiology; D010766:Phosphorylation; D024801:Tauopathies / Q000378:metabolism* / Q000473:pathology*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
C054369:MAPT protein, human; D016875:tau Proteins