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Published on: November 9, 2018
Bacopa monnieri reduces Tau aggregation and Tau-mediated toxicity in cells
Tushar Dubey1, Preeti Kushwaha2, H V Thulasiram3
1Neurobiology Group, Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, 411008 Pune, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
Abstract:
Alzheimer's disease is a neurodegenerative disease characterized by progressive memory loss and behavioral impairments. In the present study, the ethanolic extract of Bacopa monnieri was studied for its potency to inhibit Tau aggregation and rescuing of the viability of Tau-stressed cells. Bacopa monnieri was observed to inhibit the Tau aggregation in vitro. The cells exposed to Bacopa monnieri were also observed to have a low level of ROS and caspase-3 activity. The immunoblot and immunofluorescence analysis showed that Bacopa monnieri acts as an antioxidant and restored the Nrf2 levels in Neuro2a cells. Bacopa monnieri treatment to Neuro2a cells was observed to reduce the phospho-Tau load in formaldehyde-stressed cells. Furthermore, the treatment of Bacopa monnieri reduced the phosphorylation of GSK-3β in formaldehyde-stressed cells. Ran and NUP358 are the key proteins involved in nuclear transport. It was observed that formaldehyde treatment impaired the nuclear transport by missorting the NUP358 arrangement in Neuro2a cells. On the contrary, Bacopa monnieri treatment restored the NUP358 arrangement in cells. The overall results of the present study suggested that Bacopa monnieri could be considered a potent herb against Tau phosphorylation and Tau aggregation, which projects it as a promising formulation for Alzheimer's disease.
Insights
Bacopa monnieri extract inhibits Tau aggregation and phosphorylation, offering a potential natural treatment for Alzheimer's disease by protecting neuronal cells.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by memory loss and cognitive decline.
- Key pathological hallmarks of AD include Tau protein aggregation and hyperphosphorylation, leading to neuronal dysfunction.
- Identifying natural compounds with neuroprotective properties is crucial for developing novel AD therapeutics.
Purpose of the Study:
- To investigate the efficacy of ethanolic Bacopa monnieri extract in inhibiting Tau aggregation.
- To evaluate the neuroprotective effects of Bacopa monnieri in Tau-stressed neuronal cells.
- To elucidate the underlying mechanisms of Bacopa monnieri's action, including its antioxidant and anti-inflammatory properties.
Main Methods:
- In vitro assessment of Bacopa monnieri's effect on Tau aggregation.
- Cell viability assays on Tau-stressed Neuro2a cells treated with Bacopa monnieri.
- Analysis of reactive oxygen species (ROS) levels, caspase-3 activity, and Nrf2 pathway activation.
- Immunoblot and immunofluorescence techniques to assess phospho-Tau levels, GSK-3β phosphorylation, and NUP358 localization.
Main Results:
- Bacopa monnieri extract significantly inhibited Tau aggregation in vitro.
- Treatment with Bacopa monnieri reduced ROS levels and caspase-3 activity in Tau-stressed cells.
- The extract demonstrated antioxidant effects by restoring Nrf2 levels and reducing phospho-Tau load.
- Bacopa monnieri mitigated formaldehyde-induced impairment of nuclear transport by correcting NUP358 arrangement.
Conclusions:
- Bacopa monnieri exhibits potent inhibitory effects against Tau phosphorylation and aggregation.
- The herb demonstrates neuroprotective properties through antioxidant mechanisms and restoration of cellular transport.
- These findings suggest Bacopa monnieri as a promising natural agent for Alzheimer's disease management.
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