Mitochondrial Dysfunction and Oxidative and Endoplasmic Reticulum Stress in Argyrophilic Grain Disease

Ilieva, Ekaterina V.; Kichev, Anton Vladimirov; Naudí i Farré, Alba; Ferrer, Isidre; Pamplona Gras, Reinald; Portero Otín, Manuel

doi:https://doi.org/10.1097/NEN.0b013e31820f8765

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Issue date

2011

Author

Ilieva, Ekaterina V.

Kichev, Anton Vladimirov

Naudí i Farré, Alba

Ferrer, Isidre

Pamplona Gras, Reinald

Portero Otín, Manuel

Suggested citation

Ilieva, Ekaterina V.; Kichev, Anton Vladimirov; Naudí i Farré, Alba; Ferrer, Isidre; Pamplona Gras, Reinald; Portero Otín, Manuel; . (2011) . Mitochondrial Dysfunction and Oxidative and Endoplasmic Reticulum Stress in Argyrophilic Grain Disease. Journal of Neuropathology and Experimental Neurology, 2011, vol. 70, núm. 4, p. 253-263. https://doi.org/10.1097/NEN.0b013e31820f8765.

Abstract

Argyrophilic grain disease (AGD) is characterized by the accumulation of hyperphosphorylated 4R tau in dendritic varicosities (i.e."grains") in neurons and pretangles in certain areas of the cerebral cortex and other brain regions. We investigated oxidative and endoplasmic reticulum (ER) stress and dysregulation of mitochondrialbiogenesis as potential mechanisms involved in the AGD pathogenesis. Samples from AGD patients (n = 8) and nonpathologic, age-matched controls (n = 5) were compared using biochemical and immunohistochemical techniques with a panel of antibodies to markers of ER stress responses, stress chaperones, oxidative stress and associated cellular responses, respiratory chain complexes, mitochondrial regulators, and modulators of mitochondrial biogenesis. Because AGD is often associated with other tauopathies, mainly Alzheimer disease (AD), results were also compared with those of a group of similar Braak AD stage cases without grains (n = 5). In both AD and AGD cases, we found activation of key molecules that are involved in the unfolded protein response and lead to elevated ER chaperone levels, increased oxidative stress damage, mainly related to lipoxidation and targeting glycolytic enzymes. Altered expression of components of the respiratory chain markers modulating mitochondrial biogenesis were selectively affected in AGD. The findings suggest that, despite the common pathogenic trends in AD and AGD, there is molecular specificity for AGD.

URI

http://hdl.handle.net/10459.1/58645

DOI

https://doi.org/10.1097/NEN.0b013e31820f8765

Is part of

Journal of Neuropathology and Experimental Neurology, 2011, vol. 70, núm. 4, p. 253-263