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Nucleic acid oxidation in Alzheimer disease
Moreira, Paula I.; Nunomura, Akihiko; Nakamura, Masao; Takeda, Atsushi; Shenk, Justin C.; Aliev, Gjumrakch; Smith, Mark A.; Perry, GeorgeIncreasing evidence suggests that oxidative stress is intimately associated with Alzheimer disease pathophysiology. Nucleic acids (nuclear DNA, mitochondrial DNA, and RNA) are one of the several cellular macromolecules damaged by reactive oxygen species, particularly the hydroxyl radical. Because neurons are irreplaceable and survive as long as the organism does, they need elaborate defense mechanisms to ensure...
Indices of Metabolic Dysfunction and Oxidative Stress
Casadesus, Gemma; Moreira, Paula; Nunomura, Akihiko; Siedlak, Sandra; Bligh-Glover, William; Balraj, Elizabeth; Petot, Grace; Smith, Mark; Perry, GeorgeAbstract Metabolic alterations are a key player involved in the onset of Alzheimer disease pathophysiology and, in this review, we focus on diet, metabolic rate, and neuronal size differences that have all been shown to play etiological and pathological roles in Alzheimer disease. Specifically, one of the earliest manifestations of brain metabolic depression in these patients is a sustained high caloric intake...
Tau phosphorylation in Alzheimer's disease: pathogen or protector?
Lee, Hyoung-gon; Perry, George; Moreira, Paula I.; Garrett, Matthew R.; Liu, Quan; Zhu, Xiongwei; Takeda, Atsushi; Nunomura, Akihiko; Smith, Mark A.During the past decade, hypotheses concerning the pathogenesis of most neurodegenerative diseases have been dominated by the notion that the aggregation of specific proteins and subsequent formation of cytoplasmic and extracellular lesions represent a harbinger of neuronal dysfunction and death. As such, in Alzheimer's disease, phosphorylated tau protein, the major component of neurofibrillary tangles, is consi...
Redox metals and oxidative abnormalities in human prion diseases
Petersen, Robert; Siedlak, Sandra; Lee, Hyoung-Gon; Kim, Yong-Sun; Nunomura, Akihiko; Tagliavini, Fabrizio; Ghetti, Bernardino; Cras, PatrickPrion diseases are characterized by the accumulation of diffuse and aggregated plaques of protease-resistant prion protein (PrP) in the brains of affected individuals and animals. Whereas prion diseases in animals appear to be almost exclusively transmitted by infection, human prion diseases most often occur sporadically and, to a lesser extent, by inheritance or infection. In the sporadic cases (sporadic Creut...
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