ReferenceID 5390
Harmine prevents 3-nitropropionic acid-induced neurotoxicity in rats via enhancing NRF2-mediated signaling: Involvement of p21 and AMPK
Eur J Pharmacol
Oxidative stress induced neurotoxicity is increasingly perceived as an important neuropathologic mechanism underlying the motor and behavioral phenotypes associated with Huntington's disease (HD). Repeated exposure to 3-
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Record Fields
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- Reference Id
- 5390
- Evidence Id
- 21980
- Core Evidence Id
- 21980
- Source Reference Id
- 4039
- Herb2 Reference Id
- HBREF004836
- Subject Paper Key
- HBIN028803_35623405
- Pubmed Id
- 35623405
- Doi
- 10.1016/j.ejphar.2022.175046
- Paper Title
- Harmine prevents 3-nitropropionic acid-induced neurotoxicity in rats via enhancing NRF2-mediated signaling: Involvement of p21 and AMPK
- Paper Abstract
- Oxidative stress induced neurotoxicity is increasingly perceived as an important neuropathologic mechanism underlying the motor and behavioral phenotypes associated with Huntington's disease (HD). Repeated exposure to 3-nitropropionic acid (3-NP) induces neurotoxic changes which closely simulate the neuropathological and behavioral characteristics of HD. This study aimed at evaluating the prophylactic effects of the dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) inhibitor "harmine" against 3-NP-indued neurotoxicity and HD-like symptoms. The potential prophylactic effect of harmine (10 mg/kg/day; intraperitoneal) was investigated on 3-NP-induced motor and cognitive HD-like deficits, nuclear factor erythroid 2 like 2 (NRF2), AMP kinase (AMPK) and p21 protein levels and the gene expression of haem oxygenase-1 (Ho-1), NAD(P)H: quinone oxidoreductase-1 (Nqo-1) and p62 in addition to redox imbalance and histological neurotoxic changes in the striatum, prefrontal cortex, and hippocampus of male Wistar rats. Harmine successfully increased the protein levels of NRF2, AMPK and p21 and the gene expression of Ho-1, Nqo-1 and p62, restored redox homeostasis, and reduced CASPASE-3 level. This was reflected in attenuation of 3-NP-induced neurodegenerative changes and improvement of rats' motor and cognitive performance. This study draws attention to the protective role of harmine against 3-NP-induced motor and cognitive dysfunction that could be mediated via enhancing NRF2-mediated signaling with subsequent amelioration of oxidative stress injury via NRF2 activators, p21 and AMPK, in the striatum, prefrontal cortex, and hippocampus which could offer a promising therapeutic tool to slow the progression of HD.
- Journal
- Eur J Pharmacol
- Publish Year
- 2022
- Experiment Subject
- rat
- Experiment Type
- Animal Experiment
- Phenotype Related
- Huntington's Disease; Cognitive Dysfunction
- Paper Title Cn
- Paper Title En
- Harmine prevents 3-nitropropionic acid-induced neurotoxicity in rats via enhancing NRF2-mediated signaling: Involvement of p21 and AMPK
- Bilingual Status
- semi_complete