Who fans the flames of Alzheimer's disease brains? Misfolded tau on the crossroad of neurodegenerative and inflammatory pathways

Journal of Neuroinflammation

Michal Novak³  Ondrej Bugos¹  Dominika Obetkova¹  Aladar Madari²  Peter Neradil¹  Santosh Jadhav¹  Zuzana Kazmerova¹  Norbert Zilka³ 

[1] Institute of Neuroimmunology, 84510 Bratislava, Slovak Republic;Small Animals Clinic, University of Veterinary Medicine and Pharmacy, Komenskeho 73, 041 81 Kosice, Slovakia;Axon Neuroscience GmbH, 1030 Vienna, Austria

关键词: Microglia;    Neuroinflammation;    Neurofibrillary degeneration;    Tauopathies;    Alzheimer's disease;   

Others  :  1212742
DOI  :  10.1186/1742-2094-9-47

 received in 2011-10-19, accepted in 2012-03-07,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Zilka et al; licensee BioMed Central Ltd.

【 图 表 】

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