Neuroprotection against 6-OHDA toxicity in PC12 cells and mice through the Nrf2 pathway by a sesquiterpenoid from Tussilago farfara

Publication date: September 2018Source: Redox Biology, Volume 18Author(s): Joohee Lee, Kwangho Song, Eugene Huh, Myung Sook Oh, Yeong Shik KimAbstractOxidative stress plays a key role in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Therefore, the nuclear factor-E2-related factor 2 (Nrf2), a key regulator of the antioxidative response, is considered to be important as a therapeutic target for neurodegenerative diseases. We investigated the underlying mechanism of Nrf2-mediated neuroprotective effects against oxidative stress in the PC12 cell line by 7β-(3-ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), one of the sesquiterpenoids in Farfarae Flos. Pretreatment of PC12 cells with ECN had a protective effect against hydrogen peroxide (H2O2)- or 6-hydroxydopamine (6-OHDA)-induced cytotoxicity. ECN upregulated the ARE-luciferase activity and induced the mRNA expression of Nrf2 and antioxidant enzyme heme oxygenase-1 (HO-1). Knockdown of Nrf2 by small, interfering RNA (siRNA) abrogated the upregulation of HO-1, indicating that ECN had induced HO-1 via the Nrf2 pathway. Pretreatment with the thiol reducing agents, N-acetylcysteine (NAC) or dithiothreitol (DTT), attenuated Nrf2 activation and HO-1 expression. However, the non-thiol reducing antioxidant, Trolox, failed to inhibit HO-1 induction by ECN. These results suggest that ECN may directly interact with Kelch-like ECH-associated protein 1 (Keap1) and mo...
Source: Redox Biology - Category: Biology Source Type: research

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In conclusion, we focus on the various newer molecular mechanisms that are associated with the basic understanding of neuroinflammation in neurodegeneration.
Source: Neurochemistry International - Category: Neuroscience Source Type: research
A new Antimicrobial Resistance (AMR) Accelerator Programme is part of new Calls for proposals launched today by the Innovative Medicines Initiative (IMI). Of the other topics launched in the Calls, many address brain disorders (e.g. Alzheimer's disease, Parkinson's disease, Huntington's disease, major depression) and immune-mediated diseases (e.g. rheumatoid arthritis and lupus as well as inflammatory bowel diseases such as Crohn's and colitis, and skin diseases like dermatitis and psoriasis).
Source: eHealth News EU - Category: Information Technology Tags: Featured Open Calls Source Type: news
Data collected from preclinical PET scans of rhesus macaque monkeys eventually...Read more on AuntMinnie.comRelated Reading: PET imaging could help personalize cancer treatment Michael J. Fox Foundation launches $2M PET tracer prize FDG-PET predicts survival in Parkinsonian syndrome IDEAS study to explore amyloid PET and Alzheimer's PET imaging shows promise with Parkinson's
Source: Headlines - Category: Radiology Source Type: news
Abstract Heme oxygenase (HO) family catalyzes the conversion of heme into free iron, carbon monoxide and biliverdin. It possesses two well characterized isoforms: HO-1 and HO-2. Under brain physiological conditions, the expression of HO-2 is constitutive, abundant and ubiquitous, whereas HO-1 mRNA and protein are restricted to small populations of neurons and neuroglia. HO-1 is an inducible enzyme that has been shown to participate as an essential defensive mechanism for neurons exposed to oxidant challenges, being related to antioxidant defenses in certain neuropathological conditions. Considering that neurodegen...
Source: Current Pharmaceutical Design - Category: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research
MONDAY, July 16, 2018 -- Vitamin D does little to defend your brain against multiple sclerosis, Parkinson's disease or Alzheimer's disease, a new review shows. The finding is based on an analysis of more than 70 studies. " Our work counters an...
Source: - Daily MedNews - Category: General Medicine Source Type: news
Abstract Many evidences indicate that oxidative stress plays a significant role in a variety of human disease states, including neurodegenerative diseases. Iron is an essential metal for almost all living organisms due to its involvement in a large number of iron-containing proteins and enzymes, though it could be also toxic. Actually, free iron excess generates oxidative stress, particularly in brain, where anti-oxidative defences are relatively low. Its accumulation in specific regions is associated with pathogenesis in a variety of neurodegenerative diseases (i.e., Parkinson's disease, Alzheimer's disease, Hunt...
Source: Biometals - Category: Biochemistry Authors: Tags: Biometals Source Type: research
Abstract The reaction of free amino groups in proteins with reactive carbonyl species, known as glycation, leads to the formation of mixtures of products, collectively referred to as advanced glycation endproducts (AGEs). These compounds have been implicated in several important diseases, but their role in pathogenesis and clinical symptoms' development is still debated. Particularly, AGEs are often associated to the formation of amyloid deposits in conformational diseases, such as Alzheimer's and Parkinson's disease, and it has been suggested that they might influence the mechanisms and kinetics of protein aggreg...
Source: Molecular and Cellular Biochemistry - Category: Biochemistry Authors: Tags: Mol Cell Biochem Source Type: research
Abstract Disturbances in both the ability to smell and to taste are common in older persons. Such disturbances influence nutrition, safety, quality of life, and psychological and physical health. The anatomic and physiologic causes of age-related disturbances are multiple and interacting, and depend on genetic and environmental factors. Frank losses of function, distortions, and hallucinations are common. Most distortions resolve over time, although this can take months or even years. Olfactory dysfunction occurs during the earliest stages of several neurologic disorders, most notably Alzheimer's disease and Parki...
Source: The Medical Clinics of North America - Category: General Medicine Authors: Tags: Otolaryngol Clin North Am Source Type: research
(American Society for Biochemistry and Molecular Biology) Researchers at the UT Southwestern Medical Center have uncovered details of how cells invite inside corrupted proteins that can turn normal proteins corrupt, leading to neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Understanding the molecular details of how these proteins spread from cell to cell could lead to therapies to halt disease progression.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
(Bentham Science Publishers) Arranging into well-organized fibrillar aggregate, commonly known as amyloid fibril is an inherent property of any polypeptide chain. Amyloid fibrils are associated with a number of severe human pathologies like the Alzheimer's disease, Parkinson's disease, type 2 diabetes and many more. This review article includes the recent studies of identification and characterization of possible conformations of proteins which can act as aggregation precursor state (APS).
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
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