title: Who fans the flames of Alzheimer's disease brains? Misfolded tau on the crossroad of neurodegenerative and inflammatory pathways.
abstract: Neurodegeneration, induced by misfolded tau protein, and neuroinflammation, driven by glial cells, represent the salient features of Alzheimer's disease (AD) and related human tauopathies. While tau neurodegeneration significantly correlates with disease progression, brain inflammation seems to be an important factor in regulating the resistance or susceptibility to AD neurodegeneration. Previously, it has been shown that there is a reciprocal relationship between the local inflammatory response and neurofibrillary lesions. Numerous independent studies have reported that inflammatory responses may contribute to the development of tau pathology and thus accelerate the course of disease. It has been shown that various cytokines can significantly affect the functional and structural properties of intracellular tau. Notwithstanding, anti-inflammatory approaches have not unequivocally demonstrated that inhibition of the brain immune response can lead to reduction of neurofibrillary lesions. On the other hand, our recent data show that misfolded tau could represent a trigger for microglial activation, suggesting the dual role of misfolded tau in the Alzheimer's disease inflammatory cascade. On the basis of current knowledge, we can conclude that misfolded tau is located at the crossroad of the neurodegenerative and neuroinflammatory pathways. Thus disease-modified tau represents an important target for potential therapeutic strategies for patients with Alzheimer's disease.
authors.affiliation: Institute of Neuroimmunology, 84510 Bratislava, Slovak Republic.
authors.forename: Norbert
authors.initials: N
authors.lastname: Zilka
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Kazmerova
authors.forename: Santosh
authors.initials: S
authors.lastname: Jadhav
authors.forename: Peter
authors.initials: P
authors.lastname: Neradil
authors.forename: Aladar
authors.initials: A
authors.lastname: Madari
authors.forename: Dominika
authors.initials: D
authors.lastname: Obetkova
authors.forename: Ondrej
authors.initials: O
authors.lastname: Bugos
authors.forename: Michal
authors.initials: M
authors.lastname: Novak
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004660:Encephalitis / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000378:metabolism; D017510:Protein Folding; D057165:Proteostasis Deficiencies / Q000150:complications*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins