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Moscatilin Ameliorates Tau Phosphorylation and Cognitive Deficits in Alzheimer's Disease Models
Jou-Man Huang1, Fang-I Huang1, Chia-Ron Yang1
1School of Pharmacy, College of Medicine , National Taiwan University , Taipei 10050 , Taiwan.
Abstract:
Alzheimer's disease (AD) is a neurodegenerative disease and a common cause of dementia, manifesting as progressive memory loss and cognitive decline. Moscatilin, which reportedly reduces fever and is anti-inflammatory, is the bibenzyl extract from Dendrobium loddigesii. This study aimed to examine whether moscatilin ameliorates tau phosphorylation and cognitive deficits in AD models. The first in vitro AD-like model was developed by cotransfection with the pCAX FLAG APP and pRK5-EGFP-Tau P301L plasmids, resulting in the neuronal overexpression of amyloid precursor protein (APP) and tau P301L, a tauopathy-associated tau. The second model was developed by using okadaic acid to induce tau protein phosphorylation. Spatial memory/cognition was assessed using water maze and elevated plus maze tests in a scopolamine-induced mouse model, and brain slices were evaluated further by immunohistochemistry (IHC). Moscatilin significantly reduced phospho-tau expression in a concentration-dependent manner, decreased tau aggregation, and reduced apoptosis. These results indicated that moscatilin reversed tauopathy through GSK3β inactivation and inhibition of oxidative stress. Furthermore, in vivo data demonstrated that moscatilin ameliorated learning and memory impairments in mice, while IHC and Western blot results of the mouse brain confirmed that moscatilin decreased tau phosphorylation. Our novel findings suggest that moscatilin has neuroprotective effects against AD.
Insights
Moscatilin, a compound from Dendrobium loddigesii, effectively reduces tau phosphorylation and improves cognitive deficits in Alzheimer
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory loss and cognitive decline.
- Tauopathy, involving tau protein phosphorylation and aggregation, is a key pathological hallmark of AD.
- Moscatilin, a bibenzyl compound from Dendrobium loddigesii, possesses reported anti-inflammatory and antipyretic properties.
Purpose of the Study:
- To investigate the potential of moscatilin in ameliorating tau phosphorylation and cognitive deficits in Alzheimer's disease models.
- To elucidate the underlying mechanisms of moscatilin's neuroprotective effects against tauopathy.
Main Methods:
- Established in vitro Alzheimer's disease (AD) models by neuronal overexpression of amyloid precursor protein (APP) and tau P301L, and by inducing tau phosphorylation with okadaic acid.
- Utilized scopolamine-induced mouse models to assess spatial memory and cognitive function using water maze and elevated plus maze tests.
- Performed immunohistochemistry (IHC) and Western blot analyses on brain tissues to evaluate tau phosphorylation, aggregation, and apoptosis.
Main Results:
- Moscatilin significantly reduced phospho-tau expression and tau aggregation in a concentration-dependent manner.
- The compound decreased apoptosis and reversed tauopathy by inactivating GSK3β and inhibiting oxidative stress.
- In vivo studies demonstrated that moscatilin ameliorated learning and memory impairments in mice, with confirmed reduction in tau phosphorylation in brain tissues.
Conclusions:
- Moscatilin exhibits significant neuroprotective effects against Alzheimer's disease pathology.
- The compound effectively mitigates tauopathy and cognitive deficits, suggesting therapeutic potential for AD treatment.
- Moscatilin's mechanism involves GSK3β inactivation and oxidative stress inhibition, offering a novel therapeutic strategy.