Human misfolded truncated tau protein promotes activation of microglia and leukocyte infiltration in the transgenic rat model of tauopathy.
It has been hypothesized that misfolded tau protein could be a mediator of the inflammatory response in human tauopathies. Here we show that neurodegenerative lesions caused by human truncated tau promote inflammatory response manifested by upregulation of immune-molecules (CD11a,b, CD18, CD4, CD45 and CD68) and morphological activation of microglial cells in a rat model of tauopathy. In parallel, the innate immune brain response promotes activation of MHC class II positive blood-borne leukocytes and their influx into the brain parenchyma. These findings have important consequences for the rationale drug development of effective inflammation-based therapeutic strategies for human tauopathies.
Zilka
Norbert
N
Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Stozicka
Zuzana
Z
Kovac
Andrej
A
Pilipcinec
Emil
E
Bugos
Ondrej
O
Novak
Michal
M
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D049109:Cell Proliferation / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000502:physiology; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D017628:Microglia / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D017510:Protein Folding; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D055647:Rats, Transgenic; D024801:Tauopathies / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*
D000954:Antigens, Surface; D000949:Histocompatibility Antigens Class II; D016875:tau Proteins