Carnosic acid ameliorated Aβ-mediated (amyloid-β peptide) toxicity, cholinergic dysfunction and mitochondrial defect in Caenorhabditis elegans of Alzheimer's Model.

Abstract

Amyloid-β peptide (Aβ)-induced cholinergic system and mitochondrial dysfunction are major risk factors for Alzheimer's disease (AD). Our previous studies found that carnosic acid (CA), an important polyphenol antioxidant, could significantly delay Aβ1-42-mediated acute paralysis. However, many details and underlying mechanisms of CA's neuroprotection against Aβ-induced cholinergic system defects and mitochondrial dysfunction remain unclear. Herein, we deeply investigated the effects and the possible mechanisms of CA-mediated protection against Aβ toxicity in vivo through several AD Caenorhabditis elegans strains. The results showed CA delayed age-related paralysis and Aβ deposition, and significantly protected neurons from Aβ-induced toxicity. CA might downgrade the expression of ace-1 and ace-2 genes, and upregulate cha-1 and unc-17 genes to inhibit acetylcholinesterase activity and relieve Aβ-caused cholinergic system defects. Furthermore, CA might also ameliorate Aβ-induced mitochondrial imbalance and oxidative stress through up-regulating the expression of phb-1, phb-2, eat-3, and drp-1 genes. The enhancements of the cholinergic system and mitochondrial function might be the reasons for the amelioration of Aβ-mediated toxicity and Aβ aggregation mediated by CA. These findings have helped us to understand the CA anti-Aβ activity in C. elegans and the potential mechanism of action.

• Authors: Yun Chen, Yarong Wang, Qiao Qin, Yali Zhang, Lingling Xie, Jie Xiao, Yong Cao, Zuanxian Su, Yunjiao Chen
• Journal: Food & function (Food Funct) Vol. 13 Issue 8 Pg. 4624-4640 (Apr 20 2022) ISSN: 2042-650X [Electronic] England
• PMID: 35357374 (Publication Type: Journal Article)

Chemical References

• Abietanes
• Amyloid beta-Peptides
• Caenorhabditis elegans Proteins
• Cholinergic Agents
• Peptide Fragments
• Unc-17 protein, C elegans
• Vesicular Acetylcholine Transport Proteins
• Acetylcholinesterase
• salvin

Topics

• Abietanes
• Acetylcholinesterase (metabolism)
• Alzheimer Disease (chemically induced, drug therapy, genetics)
• Amyloid beta-Peptides (genetics)
• Animals
• Animals, Genetically Modified
• Caenorhabditis elegans
• Caenorhabditis elegans Proteins (genetics, metabolism)
• Cholinergic Agents (pharmacology)
• Disease Models, Animal
• Mitochondria (metabolism)
• Paralysis (chemically induced)
• Peptide Fragments (metabolism)
• Vesicular Acetylcholine Transport Proteins