Protein targets of oxidative damage in human neurodegenerative diseases with abnormal protein aggregates
MetadataShow full item record
Human neurodegenerative diseases with abnormal protein aggregates are associated with aberrant post-translational modifications, solubility, aggregation and fibril formation of selected proteins which cannot be degraded by cytosolic proteases, ubiquitin–protesome system and autophagy, and, therefore, accumulate in cells and extracellular compartments as residual debris. In addition to the accumulation of “primary” proteins, several other mechanisms are involved in the degenerative process and probably may explain crucial aspects such as the timing, selective cellular vulnerability and progression of the disease in particular individuals. One of these mechanisms is oxidative stress, which occurs in the vast majority of, if not all, degenerative diseases of the nervous system. The present review covers most of the protein targets that have been recognized as modified proteins mainly using bidimensional gel electrophoresis, Western blotting with oxidative and nitrosative markers, and identified by mass spectrometry in Alzheimer disease; certain tauopathies such as progressive supranuclear palsy, Pick disease, argyrophilic grain disease and frontotemporal lobar degeneration linked to mutations in tau protein, for example, FTLD-tau, Parkinson disease and related α-synucleinopathies; Huntington disease; and amyotrophic lateral sclerosis, together with related animal and cellular models. Vulnerable proteins can be mostly grouped in defined metabolic pathways covering glycolysis and energy metabolism, cytoskeletal, chaperoning, cellular stress responses, and members of the ubiquitin–proteasome system. Available information points to the fact that vital metabolic pathways are hampered by protein oxidative damage in several human degenerative diseases and that oxidative damage occurs at very early stages of the disease. Yet parallel functional studies are limited and further work is needed to document whether protein oxidation results in loss of activity and impaired performance. A better understanding of proteins susceptible to oxidation and nitration may serve to define damaged metabolic networks at early stages of disease and to advance therapeutic interventions to attenuate disease progression.
Is part ofBrain Pathology, 2010, vol. 20, núm. 2, p. 281-297
European research projects
Showing items related by title, author, creator and subject.
Dietary Lipid Unsaturation Influences Survival and Oxidative Modifications of an Amyotrophic Lateral Sclerosis Model in a Gender-Specific Manner Cacabelos Barral, Daniel; Ayala Jové, Ma. Victoria (Maria Victoria); Ramírez-Núñez, Omar; Granado-Serrano, Ana Belén; Boada Pallàs, Jordi; Serrano Casasola, José Carlos Enrique; Cabré Cucó, Rosanna; Nadal Rey, Gisela; Bellmunt i Curcó, Josepa; Ferrer, Isidre; Pamplona Gras, Reinald; Portero Otín, Manuel (Springer, 2014)The implication of lipid peroxidation in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) derive from high abundance of peroxidation- prone polyunsaturated fatty acids in central nervous system ...
Type-Dependent Oxidative Damage Frontotemporal Lobar Degeneration: Cortical Astrocytes Are Targets of Oxidative Damage Martínez, Anna; Carmona, Margarita; Portero Otín, Manuel; Naudí i Farré, Alba; Pamplona Gras, Reinald; Ferrer, Isidre (Oxford University Press, 2008)Oxidative injury and stress responses are common features of many neurodegenerative diseases. To assess oxidative stress responses in frontotemporal lobar degeneration (FTLD), we identified increased 4-hydroxynonenal ...
Mitochondrial ATP-Synthase in the entorhinal cortex is a target of oxidative stress at stages I/II of Alzheimer's disease pathology Terni, Beatrice; Boada Pallàs, Jordi; Portero Otín, Manuel; Pamplona Gras, Reinald; Ferrer, Isidre (Wiley, 2010)Oxidative stress has been implicated in the pathogenesis of several neurodegenerative diseases including Alzheimer's disease (AD). Several proteins have been identified as targets of oxidative damage in AD dementia (usually ...