Intraneuronal accumulation of misfolded tau protein induces overexpression of Hsp27 in activated astrocytes

Biochimica Et Biophysica Acta
Peter FilipcikMichal Novak

Abstract

Accumulation of misfolded forms of microtubule associated, neuronal protein tau causes neurofibrillary degeneration typical of Alzheimer's disease and other tauopathies. This process is accompanied by elevated cellular stress and concomitant deregulation of heat-shock proteins. We used a transgenic rat model of tauopathy to study involvement of heat shock protein 27 (Hsp27) in the process of neurofibrillary degeneration, its cell type specific expression and correlation with the amount of insoluble tau protein aggregates. The expression of Hsp27-mRNA is more than doubled and levels of Hsp27 protein tripled in aged transgenic animals with tau pathology. The data revealed a strong positive and highly significant correlation between Hsp27-mRNA and amount of sarkosyl insoluble tau. Interestingly, intracellular accumulation of insoluble misfolded tau protein in neurons was associated with overexpression of Hsp27 almost exclusively in reactive astrocytes, not in neurons. The topological dissociation of neuronally expressed pathological tau and the induction of astrocytic Hsp27, GFAP, and Vimentin along with up-regulation of microglia specific markers such as CD18, CD68 and C3 point to cooperation of astrocytes, microglia and neurons ...Continue Reading

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Citations

Oct 26, 2016·Brain Research Bulletin·Thomas ArendtMax Holzer
Feb 18, 2016·Journal of Experimental Neuroscience·Martha A Kahlson, Kenneth J Colodner
Mar 20, 2020·Biogerontology·Vittoria de Lima CamandonaJose Ribamar Ferreira-Junior

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