Overexpression of α‐synuclein decreased viability and enhanced sensitivity to prostaglandin E<sub>2</sub>, hydrogen peroxide, and a nitric oxide donor in differentiated neuroblastoma cells

Prasad, Judith E.; Kumar, Bipin; Andreatta, Cynthia; Nahreini, Piruz; Hanson, Amy J.; Yan, Xiang; Prasad, Kedar N.

doi:10.1002/jnr.20058

Cited by 20 publications

(12 citation statements)

References 36 publications

(42 reference statements)

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“…ONOO - and H 2 O 2 can each inhibit proteasomal activity, which in AD can cause APP accumulation and potentiation of OS and Aβ formation (Prasad et al, 2004). Further, 4-HNE affects proteasomal degradation by covalently adducting to cathepsin B, an integral protein in the degradation pathway (Crabb et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Oxidative and nitrative stress in neurodegeneration

Cobb

Cole

2015

Neurobiology of Disease

231

180

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Aerobes require oxygen for metabolism and normal free radical formation. As a result, maintaining the redox homeostasis is essential for brain cell survival due to their high metabolic energy requirement to sustain electrochemical gradients, neurotransmitter release, and membrane lipid stability. Further, brain antioxidant levels are limited compared to other organs and less able to compensate for reactive oxygen and nitrogen species (ROS/RNS) generation which contribute oxidative/nitrative stress (OS/NS). Antioxidant treatments such as vitamin E, minocycline, and resveratrol mediate neuroprotection by prolonging the incidence of or reversing OS and NS conditions. Redox imbalance occurs when the antioxidant capacity is overwhelmed, consequently leading to activation of alternate pathways that remain quiescent under normal conditions. If OS/NS fails to lead to adaptation, tissue damage and injury ensue, resulting in cell death and/or disease. The progression of OS/NS-mediated neurodegeneration along with contributions from microglial activation, dopamine metabolism, and diabetes comprise a detailed interconnected pathway. This review proposes a significant role for OS/NS and more specifically, lipid peroxidation (LPO) and other lipid modifications, by triggering microglial activation to elicit a neuroinflammatory state potentiated by diabetes or abnormal dopamine metabolism. Subsequently, sustained stress in the neuroinflammatory state overwhelms cellular defenses and prompts neurotoxicity resulting in the onset or amplification of brain damage.

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Section: Discussionmentioning

confidence: 99%

Oxidative and nitrative stress in neurodegeneration

Cobb

Cole

2015

Neurobiology of Disease

231

180

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“…5 Although the majority of PD cases are sporadic, several studies have reported familial forms of the disease caused by point mutations [27][28][29] and multiplications 30,31 in genes that encode for proteins such as alpha-synuclein, parkin, 32 and DJ-1 33 that lead to nigrostriatal DA neurons degeneration and death, formation of protein aggregates, functional impairments of the ubiquitin-proteasome system, 34 mitochondrial dysfunction, 35 and oxidative stress. 36 Alpha-synuclein, a 14 kDa protein expressed in the presynaptic terminals of neurons, participates in synaptic vesicle recycling and dopaminergic neurotransmission. 37 The discovery that alpha-synuclein protein is a major component of Lewy bodies and Lewy neuritis in PD and that mutated alpha-synuclein has a tendency to misfold and aggregate, indicate that alpha-synuclein is a key element in the development of PD.…”

Section: Oxidative Stress In Pdmentioning

confidence: 99%

Cellular and molecular mechanisms of antioxidants in Parkinson's disease

Sutachán

Casas

Albarracín

et al. 2012

Nutritional Neuroscience

105

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Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by the degeneration and progressive loss of dopaminergic neurons in the substantia nigra pars compacta. It has been suggested that oxidative stress plays a role in the etiology and progression of PD. For instance, low levels of endogenous antioxidants, increased reactive species, augmented dopamine oxidation, and high iron levels have been found in brains from PD patients. In vitro and in vivo studies of Parkinson models evaluating natural and endogenous antioxidants such as polyphenols, coenzyme Q10, and vitamins A, C, and E have shown protective effects against oxidative-induced neuronal death. In this paper, we will review the mechanisms by which polyphenols and endogenous antioxidants can produce protection. Some of the mechanisms reviewed include: scavenging nitrogen and oxygen reactive species, regulation of signaling pathways associated with cell survival and inflammation, and inhibition of synphilin-1 and alpha-synuclein aggregation.

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“…cDNA synthesis was carried out as previously described using 2 g total RNA [35]. Real time PCR was performed using LightCycler FastStart DNA Master SYBR Green I reaction mix as previously described [36]. Primers used to detect ␣-synuclein and S29 (housekeeping gene) transcripts were as follows: ␣-synuclein 5Ј-TCCATAGAAGACACCGGG-Ј3; 5Ј-GCT-GAGAAGACCAAAGAGCAA-Ј3; S29 5Ј-AAGGCAAGAT-GGGTCACCAGCAGCTCTA-Ј3 and 5Ј-TACAAAGACTAG-CATGATCGGTTCCACT-Ј3.…”

Section: Rna Isolation and Rt-pcrmentioning

confidence: 99%