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

被引:16
作者
Ilieva, Ekaterina V. [1 ]
Kichev, Anton [1 ]
Naudi, Alba [1 ]
Ferrer, Isidre [2 ]
Pamplona, Reinald [1 ]
Portero-Otin, Manuel [1 ]
机构
[1] Univ Lleida Irblleida, Dept Expt Med, Lleida 25008, Spain
[2] Inst Neuropathol, Barcelona, Spain
关键词
Argyrophilic grain disease; Endoplasmic reticulum stress; Mitochondrial dysfunction; Neurodegeneration; Oxidative stress; Proteomics; Unfolded protein response; UNFOLDED PROTEIN RESPONSE; TRANSLATIONAL CONTROL; SIGNALING PATHWAY; BIOGENESIS; KINASES; DAMAGE; NEURODEGENERATION; IDENTIFICATION; PGC-1-ALPHA; GENERATION;
D O I
10.1097/NEN.0b013e31820f8765
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 mitochondrial biogenesis 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.
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收藏
页码:253 / 263
页数:11
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