Protective effects of Peroxiredoxin 6 overexpression on amyloid β-induced apoptosis in PC12 cells.
ABSTRACT Abstract Oxidative stress triggered by amyloid β (Aβ) accumulation contributes substantially to the pathogenesis of Alzheimer's disease (AD). In the present study, we examined the involvement of the antioxidant activity of peroxiredoxin 6 (Prdx 6) in protecting against Aβ25-35-induced neurotoxicity in rat PC12 cells. Treatment of PC12 cells with Aβ25-35 resulted in a dose- and time-dependent cytotoxicity that was associated with increased accumulation of intracellular reactive oxygen species (ROS) and mitochondria-mediated apoptotic cell death, including activation of caspase 3/9, inactivation of poly ADP-ribosyl polymerse (PARP), and dysregulation of Bcl-2 and Bax. This apoptotic signaling machinery was markedly attenuated in PC12 cells that overexpress wild-type Prdx 6, but not in cells that overexpress the C47S catalytic mutant of Prdx 6. This indicates that the peroxidase activity of Prdx 6 protects PC12 cells from Aβ25-35-induced neurotoxicity. The neuroprotective role of the antioxidant Prdx 6 suggests its therapeutic and/or prophylactic potential to slow the progression of AD and limit the extent of neuronal cell death caused by AD.
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ABSTRACT: This review provides an overview of the biochemistry of thiol redox couples and the significance of thiol redox homeostasis in neurodegenerative disease. The discussion is centred on cysteine/cystine redox balance, the significance of the xc(-) cystine-glutamate exchanger and the association between protein thiol redox balance and neurodegeneration, with particular reference to Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and glaucoma. The role of thiol disulphide oxidoreductases in providing neuroprotection is also discussed. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.04/2015; 5:186-194. DOI:10.1016/j.redox.2015.04.004
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ABSTRACT: On a global basis, at least 15 million individuals suffer some form of a stroke every year. Of these individuals, approximately 800,000 of these cerebrovascular events occur in the United States (US) alone. The incidence of stroke in the US has declined from the third leading cause of death to the fourth, a result that can be attributed to multiple factors that include improved vascular disease management, reduced tobacco use, and more rapid time to treatment in patients that are clinically appropriate to receive recombinant tissue plasminogen activator. However, treatment strategies for the majority of stroke patients are extremely limited and represent a critical void for care. A number of new therapeutic considerations for stroke are under consideration, but it is the mammalian target of rapamycin (mTOR) that is receiving intense focus as a potential new target for cerebrovascular disease. As part of the phosphoinositide 3-kinase (PI 3-K) and protein kinase B (Akt) cascade, mTOR is an essential component of mTOR Complex 1 (mTORC1) and mTOR Complex 2 (mTORC2) to govern cell death involving apoptosis, autophagy, and necroptosis, cellular metabolism, and gene transcription. Vital for the consideration of new therapeutic strategies for stroke is the ability to understand how the intricate and complex pathways of mTOR signaling sometimes lead to disparate clinical outcomes.Current neurovascular research 04/2014; DOI:10.2174/1567202611666140408104831 · 2.74 Impact Factor
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ABSTRACT: Alzheimer's disease (AD) is a devastative neurodegenerative disorder with complex etiology. Apoptosis, a biological process that plays an essential role in normal physiology to oust a few cells and contribute to the normal growth, when impaired or influenced by various factors such as Bcl2, Bax, caspases, amyloid beta, tumor necrosis factor-α, amyloid precursor protein intracellular C-terminal domain, reactive oxygen species, perturbation of enzymes leads to deleterious neurodegenerative disorders like AD. There are diverse pathways that provoke manifold events in mitochondria and endoplasmic reticulum (ER) to execute the process of cell death. This review summarizes the crucial apoptotic mechanisms occurring in both mitochondria and ER. It gives substantial summary of the diverse mechanisms studied in vivo and in vitro. A brief account on neuroprotection of several bioactive components, flavonoids and antioxidants of plants against apoptotic events of both mitochondria and ER in both in vitro and in vivo has been discussed. In light of this, the burgeoning need to develop animal models to study the efficacy of various therapeutic effects has been accentuated.Neurochemical Research 10/2014; 39(12). DOI:10.1007/s11064-014-1454-4 · 2.55 Impact Factor