Depletion of oxidative and endoplasmic reticulum stress regulators in Pick disease
Ilieva, Ekaterina V.
Kichev, Anton Vladimirov
MetadataShow full item record
Both oxidative and endoplasmic reticulum (ER) stress is associated with multiple neurodegenerative, age-related diseases. The rare disorder Pick disease (PiD) shares some pathological hallmarks of other neurodegenerative diseases that may be related to oxidative stress. Importantly, activation of an ER stress response, which is also involved in aging, has not yet been investigated in PiD. In this study, we assessed the implication of ER stress associated with oxidative stress in PiD as a potential mechanism involved in its pathogenesis. Samples from morphologically affected frontal cortex and apparently pathologically preserved occipital cortex showed region-dependent increases in different protein oxidative damage pathways. The oxidative modifications targeted antioxidant enzymes, proteases, heat shock proteins, and synaptic proteins. These effects were associated with compromised proteasomal function and ER stress in frontal cortex samples. In addition, we observed a depletion in ER chaperones (glucose-regulated proteins Grp78/BiP and glucose-regulated protein 94) and differences in tissue content and distribution of nuclear factor-erythroid 2 p45-related respiratory 2, required for cell survival during the unfolded protein response. These results demonstrate increased region-specific protein oxidative damage in PiD, with proteasomal alteration and dysfunctional ER stress response. We suggest this was caused by complete and specific depletion of Grp78/BiP, contributing to the pathophysiology of this neurodegenerative disease.
Is part ofFree Radical Biology and Medicine, 2010, vol. 48, núm. 10, p. 1302-1310
European research projects
Showing items related by title, author, creator and subject.
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 (Oxford University Press, 2011)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 ...
Cabré Cucó, Rosanna; Naudí i Farré, Alba; Dominguez Gonzalez, Mayelin; Ayala Jové, Ma. Victoria (Maria Victoria); Jové Font, Mariona; Mota Martorell, Natàlia; Piñol Ripoll, Gerard; Gil Villar, M. Pilar; Rué i Monné, Montserrat; Portero Otín, Manuel; Ferrer, Isidre; Pamplona Gras, Reinald (Elsevier, 2017)Human brain aging is the physiological process which underlies as cause of cognitive decline in the elderly and the main risk factor for neurodegenerative diseases such as Alzheimer's disease. Human neurons are functional ...
Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance Fourcade, Stéphane; Morató, Laia; Parameswaran, Janani; Ruiz, Montserrat; Ruiz-Cortés, Tatiana; Jové Font, Mariona; Naudí i Farré, Alba; Martínez, Paloma; Dierssen, Mara; Ferrer, Isidre; Villarroya, Francesc; Pamplona Gras, Reinald; Vaquero, Alejandro; Portero Otín, Manuel; Pujol, Aurora (Wiley, 2017)Sirtuin 2 (SIRT2) is a member of a family of NAD+-dependent histone deacetylases (HDAC) that play diverse roles in cellular metabolism and especially for aging process. SIRT2 is located in the nucleus, cytoplasm, and ...