Oxidative stress, neurodegeneration, and the balance of protein degradation and protein synthesis

Dasuri, Kalavathi; Zhang, Le; Keller, Jeffrey N.

doi:10.1016/j.freeradbiomed.2012.09.016

Cited by 323 publications

(289 citation statements)

References 260 publications

Supporting

Mentioning

277

Contrasting

Unclassified

Order By: Relevance

“…The neuronal populations that are most affected in PD accumulate oxidized lipids, proteins, and DNA [1]. These markers of oxidative damage are accompanied by reduced levels of the major cellular antioxidant, glutathione (GSH), which is used by cells to both scavenge reactive oxygen species (ROS) and repair oxidized protein residues [2]. A causal role for oxidative stress and GSH depletion in PD is supported by both clinical and animal studies [1,[3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Neuronal Glutathione Content and Antioxidant Capacity can be Normalized In Situ by N-acetyl Cysteine Concentrations Attained in Human Cerebrospinal Fluid

et al. 2016

View full text Add to dashboard Cite

N-acetyl cysteine (NAC) supports the synthesis of glutathione (GSH), an essential substrate for fast, enzymatically catalyzed oxidant scavenging and protein repair processes. NAC is entering clinical trials for adrenoleukodystrophy, Parkinson's disease, schizophrenia, and other disorders in which oxidative stress may contribute to disease progression. However, these trials are hampered by uncertainty about the dose of NAC required to achieve biological effects in human brain. Here we describe an approach to this issue in which mice are used to establish the levels of NAC in cerebrospinal fluid (CSF) required to affect brain neurons. NAC dosing in humans can then be calibrated to achieve these NAC levels in human CSF. The mice were treated with NAC over a range of doses, followed by assessments of neuronal GSH levels and neuronal antioxidant capacity in ex vivo brain slices. Neuronal GSH levels and antioxidant capacity were augmented at NAC doses that produced peak CSF NAC concentrations of ≥50 nM. Oral NAC administration to humans produced CSF concentrations of up to 10 μM, thus demonstrating that oral NAC administration can surpass the levels required for biological activity in brain. Variations of this approach may similarly facilitate and rationalize drug dosing for other agents targeting central nervous system disorders.

show abstract

Section: Introductionmentioning

confidence: 99%

Neuronal Glutathione Content and Antioxidant Capacity can be Normalized In Situ by N-acetyl Cysteine Concentrations Attained in Human Cerebrospinal Fluid

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Autophagy Advances in Geriatrics 5 acts as a starvation response to maintain cellular nutrient levels and helps to regulate intracellular organelle homeostasis. Autophagy plays a crucial role in the removal of toxic/aggregate proteins and impaired organelles that could damage cells during stress and its alteration is reported in various human pathologies including neurodegenerative, cancers, and lysosomal storage disorders [54,55]. Autophagy includes three major types: macroautophagy (indicated simply as autophagy), microautophagy, and chaperone-mediated autophagy (CMA).…”

Section: 4mentioning

confidence: 99%

“…Once the autophagosomes fuse with the lysosomes, their cargo is degraded by the lysosomal hydrolases. Acidification of the newly formed autolysosomes is needed for activation of the lysosomal hydrolases and effective proteolysis of substrates, and it is mediated by a vacuolar [H+] ATPase (v-ATPase) [55,61,62].…”

Section: 4mentioning

confidence: 99%

See 1 more Smart Citation

Oxidative Stress and Proteostasis Network: Culprit and Casualty of Alzheimer’s-Like Neurodegeneration

Domenico

Head

Butterfield

et al. 2014

Advances in Geriatrics

View full text Add to dashboard Cite

Free radical-mediated damage to proteins is particularly important in aging and age-related neurodegenerative diseases, because in the majority of cases it is a non-reversible phenomenon that requires clearance systems for removal. Major consequences of protein oxidation are loss of protein function and the formation of large protein aggregates, which are often toxic to cells if allowed to accumulate. Deposition of aggregated, misfolded, and oxidized proteins may also result from the impairment of protein quality control (PQC) system, including protein unfolded response, proteasome, and autophagy. Perturbations of such components of the proteostasis network that provides a critical protective role against stress conditions are emerging as relevant factor in triggering neuronal death. In this outlook paper, we discuss the role of protein oxidation as a major contributing factor for the impairment of the PQC regulating protein folding, surveillance, and degradation. Recent studies from our group and from others aim to better understand the link between Down syndrome and Alzheimer's disease neuropathology. We propose oxidative stress and alteration of proteostasis network as a possible unifying mechanism triggering neurodegeneration.

show abstract

“…They are known as oxidants and prooxidants [1,2]. The imbalance between ROS and antioxidants can cause oxidative stress, which can induce peroxidation of cell membranes, oxidation to essential macromolecules such as -proteins and DNA, inhibition to the electron transport chain in mitochondria [3]. Molecules that inhibit or prevent the oxidation of other molecules are termed as antioxidants.…”

Section: Introductionmentioning

confidence: 99%

Net effects of cashew nuts in Saccharomyces cerevisiae front to damage induced by hydrogen peroxide

Leite¹,

Gomes²,

Oliveira³

et al. 2016

Int Arch Med

View full text Add to dashboard Cite

Cellular injury associated with oxidative stress has been related in the etiology and progression of many diseases, including neurodegenerative diseases and cancer. Shell of cashew nut releases the alkylphenols oil, known as cashew nut shell liquid (CNSL), which can be characterized according to the method of production such as technical (tCNSL) and in natural (iCNSL) types. This study aimed to characterize the chemical constituents in both liquids by gas chromatography coupled to mass spectrometry (GC-MS), and to evaluate the net effect of them in proficient (SODWT) and deficient (Sod1∆, Sod2∆, Cat1∆, Sod1∆Sod2∆, Sod1∆Cat1∆) Saccharomyces cerevisiae oxidative damaged induced by hydrogen peroxide (H 2 O 2 (10 mM); stressor) at concentrations of 17.37, 34.7 and 69.5 µg/ml in pre-, co-and post-treatment. Both iCNSL and tCNSL produced no oxidizing effect to the tested yeast strains, otherwise they protected against damage induced by stressor (STR). However, tCNSL was found more prominent than the iCNSL in restorative activity. In conclusion, CNSLs (iCNSL/tCNSL) exhibited excellent protective, antioxidant and repair capabilities compared to the damage induced by STR in S. cerevisiae cells, thus may be a suggestion for its biotechnological production especially for pharmaceutical account.

show abstract

Oxidative stress, neurodegeneration, and the balance of protein degradation and protein synthesis

Cited by 323 publications

References 260 publications

Neuronal Glutathione Content and Antioxidant Capacity can be Normalized In Situ by N-acetyl Cysteine Concentrations Attained in Human Cerebrospinal Fluid

Neuronal Glutathione Content and Antioxidant Capacity can be Normalized In Situ by N-acetyl Cysteine Concentrations Attained in Human Cerebrospinal Fluid

Oxidative Stress and Proteostasis Network: Culprit and Casualty of Alzheimer’s-Like Neurodegeneration

Net effects of cashew nuts in Saccharomyces cerevisiae front to damage induced by hydrogen peroxide

Contact Info

Product

Resources

About