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Insulin and Insulin-Sensitizing Drugs in Neurodegeneration: Mitochondria as The...
Cardoso, Susana; Santos, Renato; Correia, Sonia; Carvalho, Cristina; Zhu, Xiongwei; Lee, Hyoung-Gon; Casadesu, Gemma; Smith, Mark A.; Perry, GeorgeInsulin, besides its glucose lowering effects, is involved in the modulation of lifespan, aging and memory and learning processes. As the population ages, neurodegenerative disorders become epidemic and a connection between insulin signaling dysregulation, cognitive decline and dementia has been established. Mitochondria are intracellular organelles that despite playing a critical role in cellular metabolism ar...
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...
Iron: The Redox-active Center of Oxidative Stress in Alzheimer Disease
Castellani, Rudy; Moreira, Paula; Liu, Gang; Dobson, Jon; Perry, George; Smith, Mark; Zhu, XiongweiAbstract Although iron is essential in maintaining the function of the central nervous system, it is a potent source of reactive oxygen species. Excessive iron accumulation occurs in many neurodegenerative diseases including Alzheimer disease (AD), Parkinson’s disease, and Creutzfeldt-Jakob disease, raising the possibility that oxidative stress is intimately involved in the neurodegenerative process. AD in par...
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...
Lipoic acid and N-acetyl cysteine decrease mitochondrial-related oxidative stre...
Moreira, Paula I.; Harris, Peggy L. R.; Zhu, Xiongwei; Santos, Maria S.; Oliveira, Catarina R.; Smith, Mark A.; Perry, GeorgeIn this study, we evaluated the effect of lipoic acid (LA) and N-acetyl cysteine (NAC) on oxidative [4-hydroxy-2-nonenal, N(epsilon)-(carboxymethyl)lysine and heme oxygenase-1] and apoptotic (caspase 9 and Bax) markers in fibroblasts from patients with Alzheimer disease (AD) and age-matched and young controls. AD fibroblasts showed the highest levels of oxidative stress, and the antioxidants, lipoic acid (1 mM)...
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...
Ciprofloxacin Does Not Exert Nephrotoxicity in Rats
Baykal, Asli; Sarigül, Figen; Süleymanlar, Gültekin; Moreira, Paula I.; Perry, George; Smith, Mark A.; Alicigüzel, YakupCiprofloxacin, a member of the fluoroquinolone class, is an antibiotic used as a treatment for infections including the Anthrax bacteria. Studies concerning the safety and efficacy of ciprofloxacin have been controversial with respect to nephrotoxicity. Using rats orally treated with ciprofloxacin (400mg/kg/d), the effects of this drug were analyzed measuring several indications of nephrotoxicity: -NAG, creatin...
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