Protective effects of 3-alkyl luteolin derivatives are mediated by Nrf2 transcriptional activity and decreased oxidative stress in Huntington's disease mouse striatal cells

2015 ◽  
Vol 91 ◽  
pp. 1-12 ◽  
Author(s):  
Ana M. Oliveira ◽  
Susana M. Cardoso ◽  
Márcio Ribeiro ◽  
Raquel S.G.R. Seixas ◽  
Artur M.S. Silva ◽  
...  
Neuroreport ◽  
2012 ◽  
Vol 23 (1) ◽  
pp. 10-15 ◽  
Author(s):  
Antonio Valencia ◽  
Ellen Sapp ◽  
Patrick B. Reeves ◽  
Jonathan Alexander ◽  
Nicholas Masso ◽  
...  

2018 ◽  
Vol 115 (30) ◽  
pp. E7081-E7090 ◽  
Author(s):  
Laura E. Bowie ◽  
Tamara Maiuri ◽  
Melanie Alpaugh ◽  
Michelle Gabriel ◽  
Nicolas Arbez ◽  
...  

The huntingtin N17 domain is a modulator of mutant huntingtin toxicity and is hypophosphorylated in Huntington’s disease (HD). We conducted high-content analysis to find compounds that could restore N17 phosphorylation. One lead compound from this screen was N6-furfuryladenine (N6FFA). N6FFA was protective in HD model neurons, and N6FFA treatment of an HD mouse model corrects HD phenotypes and eliminates cortical mutant huntingtin inclusions. We show that N6FFA restores N17 phosphorylation levels by being salvaged to a triphosphate form by adenine phosphoribosyltransferase (APRT) and used as a phosphate donor by casein kinase 2 (CK2). N6FFA is a naturally occurring product of oxidative DNA damage. Phosphorylated huntingtin functionally redistributes and colocalizes with CK2, APRT, and N6FFA DNA adducts at sites of induced DNA damage. We present a model in which this natural product compound is salvaged to provide a triphosphate substrate to signal huntingtin phosphorylation via CK2 during low-ATP stress under conditions of DNA damage, with protective effects in HD model systems.


Author(s):  
Ravi Ranjan Kumar ◽  
Lovekesh Singh ◽  
Amandeep Thakur ◽  
Shamsher Singh ◽  
Bhupinder Kumar

Background: Vitamins are the micronutrients required for boosting the immune system and managing any future infection. Vitamins are involved in neurogenesis, a defense mechanism working in neurons, metabolic reactions, neuronal survival, and neuronal transmission. Their deficiency leads to abnormal functions in the brain like oxidative stress, mitochondrial dysfunction, accumulation of proteins (synuclein, Aβ plaques), neurodegeneration, and excitotoxicity. Methods: In this review, we have compiled various reports collected from PubMed, Scholar Google, Research gate, and Science direct. The findings were evaluated, compiled, and represented in this manuscript. Conclusion: The deficiency of vitamins in the body causes various neurological disorders like Alzheimer’s disease, Parkinson’s disease, Huntington's disease, and depression. We have discussed the role of vitamins in neurological disorders and the normal human body. Depression is linked to a deficiency of vitamin-C and vitamin B. In the case of Alzheimer’s disease, there is a lack of vitamin-B1, B12, and vitamin-A, which results in Aβ-plaques. Similarly, in Parkinson’s disease, vitamin-D deficiency leads to a decrease in the level of dopamine, and imbalance in vitamin D leads to accumulation of synuclein. In MS, Vitamin-C and Vitamin-D deficiency causes demyelination of neurons. In Huntington's disease, vitamin- C deficiency decreases the antioxidant level, enhances oxidative stress, and disrupts the glucose cycle. Vitamin B5 deficiency in Huntington's disease disrupts the synthesis of acetylcholine and hormones in the brain.


2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Svetlana A. Ivanova ◽  
Anton J. M. Loonen

A serendipitous pharmacogenetic finding links the vulnerability to developing levodopa-induced dyskinesia to the age of onset of Huntington’s disease. Huntington’s disease is caused by a polyglutamate expansion of the protein huntingtin. Aberrant huntingtin is less capable of binding to a member of membrane-associated guanylate kinase family (MAGUKs): postsynaptic density- (PSD-) 95. This leaves more PSD-95 available to stabilize NR2B subunit carrying NMDA receptors in the synaptic membrane. This results in increased excitotoxicity for which particularly striatal medium spiny neurons from the indirect extrapyramidal pathway are sensitive. In Parkinson’s disease the sensitivity for excitotoxicity is related to increased oxidative stress due to genetically determined abnormal metabolism of dopamine or related products. This probably also increases the sensitivity of medium spiny neurons for exogenous levodopa. Particularly the combination of increased oxidative stress due to aberrant dopamine metabolism, increased vulnerability to NMDA induced excitotoxicity, and the particular sensitivity of indirect pathway medium spiny neurons for this excitotoxicity may explain the observed increased prevalence of levodopa-induced dyskinesia.


2015 ◽  
Vol 89 ◽  
pp. 1085-1096 ◽  
Author(s):  
Adriana Covarrubias-Pinto ◽  
Pablo Moll ◽  
Macarena Solís-Maldonado ◽  
Aníbal I. Acuña ◽  
Andrea Riveros ◽  
...  

2016 ◽  
Vol 87 (Suppl 1) ◽  
pp. A16.3-A17
Author(s):  
Meera Purushottam ◽  
Sowmya Devatha Venkatesh ◽  
Nikhil Ratna ◽  
Somdatta Sen ◽  
Lakshminarayanan Kota ◽  
...  

2012 ◽  
Vol 87 (4-5) ◽  
pp. 397-405 ◽  
Author(s):  
Dirleise Colle ◽  
Juliana M. Hartwig ◽  
Félix A. Antunes Soares ◽  
Marcelo Farina

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