The critical role of methionine 35 in Alzheimer's amyloid β-peptide (1–42)-induced oxidative stress and neurotoxicity

2005 ◽  
Vol 1703 (2) ◽  
pp. 149-156 ◽  
Author(s):  
D. Allan Butterfield ◽  
Debra Boyd-Kimball
Keyword(s):  
Oxidative Stress ◽  
Critical Role ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Methionine 35

scholarly journals In vivo oxidative stress in brain of Alzheimer disease transgenic mice: Requirement for methionine 35 in amyloid β-peptide of APP

2010 ◽  
Vol 48 (1) ◽  
pp. 136-144 ◽  
Author(s):  
D. Allan Butterfield ◽  
Veronica Galvan ◽  
Miranda Bader Lange ◽  
Huidong Tang ◽  
Renã A. Sowell ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer Disease ◽  
Transgenic Mice ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Methionine 35

scholarly journals The role of mitochondria-targeted antioxidant MitoQ in neurodegenerative disease

2018 ◽  
pp. 1-8
Author(s):  
Linlin Zhang ◽  
Aurelio Reyes ◽  
Xiangdong Wang
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Mitochondrial Dysfunction ◽  
Neurodegenerative Disease ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
And Oxidative Stress

Abstract: The discovery of charged molecules being able to cross the mitochondrial membrane has prompted many scholars to exploit this idea to find a way of preventing or slowing down aging. In this paper, we will focus on mitochondriatargeted antioxidants, which are cationic derivatives of plastoquinone, and in particular on the mitochondria-targeted antioxidant therapy of neurodegenerative diseases. It is well known that the accumulation of amyloid-β peptide (Aβ) in mitochondria and its related mitochondrial dysfunction are critical signatures of Alzheimer’ s disease (AD). In another neurodegenerative disease, Parkinson’s disease (PD), the loss of dopaminergic neurons in the substantia nigra and the production of Lewy bodies are among their pathological features. Pathogenesis of Parkinson’s disease and Alzheimer’s disease has been frequently linked to mitochondrial dysfunction and oxidative stress. Recent studies show that MitoQ, a mitochondria-targeted antioxidant, may possess therapeutic potential for Aβ-related and oxidative stress-associated neurodegenerative diseases, especially AD. Although MitoQ has been developed to the stage of clinical trials in PD, its true clinical effect still need further verification. This review aims to discuss the role of mitochondrial pathology in neurodegenerative diseases, as well as the recent development of mitochondrial targeted antioxidants as a potential treatment for these diseases by removing excess oxygen free radicals and inhibiting lipid peroxidation in order to improve mitochondrial function.  

scholarly journals Phosphorylation of p66Shc and forkhead proteins mediates Aβ toxicity

2005 ◽  
Vol 169 (2) ◽  
pp. 331-339 ◽  
Author(s):  
Wanli W. Smith ◽  
Darrell D. Norton ◽  
Myriam Gorospe ◽  
Haibing Jiang ◽  
Shino Nemoto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Redox Regulation ◽  
Critical Role ◽  
Ectopic Expression ◽  
Amyloid Β ◽  
Dominant Negative ◽  
Neuronal Cultures ◽  
Amyloid Β Peptide ◽  
Dependent Manner ◽  
Primary Neuronal Cultures

Excessive accumulation of amyloid β-peptide (Aβ) plays an early and critical role in synapse and neuronal loss in Alzheimer's Disease (AD). Increased oxidative stress is one of the mechanisms whereby Aβ induces neuronal death. Given the lessened susceptibility to oxidative stress exhibited by mice lacking p66Shc, we investigated the role of p66Shc in Aβ toxicity. Treatment of cells and primary neuronal cultures with Aβ caused apoptotic death and induced p66Shc phosphorylation at Ser36. Ectopic expression of a dominant-negative SEK1 mutant or chemical JNK inhibition reduced Aβ-induced JNK activation and p66Shc phosphorylation (Ser36), suggesting that JNK phosphorylates p66Shc. Aβ induced the phosphorylation and hence inactivation of forkhead transcription factors in a p66Shc-dependent manner. Ectopic expression of p66ShcS36A or antioxidant treatment protected cells against Aβ-induced death and reduced forkhead phosphorylation, suggesting that p66Shc phosphorylation critically influences the redox regulation of forkhead proteins and underlies Aβ toxicity. These findings underscore the potential usefulness of JNK, p66Shc, and forkhead proteins as therapeutic targets for AD.

The role of oxidative stress in the toxicity induced by amyloid β-peptide in Alzheimer’s disease

2000 ◽  
Vol 62 (6) ◽  
pp. 633-648 ◽  
Author(s):  
Soledad Miranda ◽  
Carlos Opazo ◽  
Luis F Larrondo ◽  
Francisco J Muñoz ◽  
Francisca Ruiz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Amyloid Β Peptide

scholarly journals Quercetin Disaggregates Prion Fibrils and Decreases Fibril-Induced Cytotoxicity and Oxidative Stress

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1081
Author(s):  
Kun-Hua Yu ◽  
Cheng-I Lee
Keyword(s):  
Oxidative Stress ◽  
Prion Protein ◽  
Amyloid Fibrils ◽  
Neuroblastoma Cells ◽  
Amyloid Β ◽  
Transmissible Spongiform Encephalopathies ◽  
Amyloid Β Peptide ◽  
Hemolysis Assay ◽  
Spongiform Encephalopathies

Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases caused by misfolding and aggregation of prion protein (PrP). Previous studies have demonstrated that quercetin can disaggregate some amyloid fibrils, such as amyloid β peptide (Aβ) and α-synuclein. However, the disaggregating ability is unclear in PrP fibrils. In this study, we examined the amyloid fibril-disaggregating activity of quercetin on mouse prion protein (moPrP) and characterized quercetin-bound moPrP fibrils by imaging, proteinase resistance, hemolysis assay, cell viability, and cellular oxidative stress measurements. The results showed that quercetin treatment can disaggregate moPrP fibrils and lead to the formation of the proteinase-sensitive amorphous aggregates. Furthermore, quercetin-bound fibrils can reduce the membrane disruption of erythrocytes. Consequently, quercetin-bound fibrils cause less oxidative stress, and are less cytotoxic to neuroblastoma cells. The role of quercetin is distinct from the typical function of antiamyloidogenic drugs that inhibit the formation of amyloid fibrils. This study provides a solution for the development of antiamyloidogenic therapy.

Role of Phenylalanine 20 in Alzheimer's Amyloid β-Peptide (1-42)-Induced Oxidative Stress and Neurotoxicity

2004 ◽  
Vol 17 (12) ◽  
pp. 1743-1749 ◽  
Author(s):  
Debra Boyd-Kimball ◽  
Hafiz Mohmmad Abdul ◽  
Tanea Reed ◽  
Rukhsana Sultana ◽  
D. Allan Butterfield
Keyword(s):  
Oxidative Stress ◽  
Amyloid Β ◽  
Amyloid Β Peptide
Sign in / Sign up

Export Citation Format

Share Document