Cargando…
Cannabidiol Enhances Microglial Beta-Amyloid Peptide Phagocytosis and Clearance via Vanilloid Family Type 2 Channel Activation
Alzheimer’s disease (AD) is associated with the accumulation and aggregation of amyloid in the brain. The cation channel TRPV2 may mediate the pathological changes in mild cognitive impairment. A high-affinity agonist of TRPV2 named cannabidiol is one of the candidate drugs for AD. However, the mole...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140666/ https://www.ncbi.nlm.nih.gov/pubmed/35628181 http://dx.doi.org/10.3390/ijms23105367 |
_version_ | 1784715153961385984 |
---|---|
author | Yang, Shaobin Du, Yaqin Zhao, Xiaoqian Tang, Qi Su, Wei Hu, Yuemeng Yu, Peng |
author_facet | Yang, Shaobin Du, Yaqin Zhao, Xiaoqian Tang, Qi Su, Wei Hu, Yuemeng Yu, Peng |
author_sort | Yang, Shaobin |
collection | PubMed |
description | Alzheimer’s disease (AD) is associated with the accumulation and aggregation of amyloid in the brain. The cation channel TRPV2 may mediate the pathological changes in mild cognitive impairment. A high-affinity agonist of TRPV2 named cannabidiol is one of the candidate drugs for AD. However, the molecular mechanism of cannabidiol via TRPV2 in AD remains unknown. The present study investigated whether cannabidiol enhances the phagocytosis and clearance of microglial Aβ via the TRPV2 channel. We used a human dataset, mouse primary neuron and microglia cultures, and AD model mice to evaluate TRPV2 expression and the ability of microglial amyloid-β phagocytosis in vivo and in vitro. The results revealed that TRPV2 expression was reduced in the cortex and hippocampus of AD model mice and AD patients. Cannabidiol enhanced microglial amyloid-β phagocytosis through TRPV2 activation, which increased the mRNA expression of the phagocytosis-related receptors, but knockdown of TRPV2 or Trem2 rescued the expression. TRPV2-mediated effects were also dependent on PDK1/Akt signaling, a pathway in which autophagy was indispensable. Furthermore, cannabidiol treatment successfully attenuated neuroinflammation while simultaneously improving mitochondrial function and ATP production via TRPV2 activation. Therefore, TRPV2 is proposed as a potential therapeutic target in AD, while CBD is a promising drug candidate for AD. |
format | Online Article Text |
id | pubmed-9140666 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91406662022-05-28 Cannabidiol Enhances Microglial Beta-Amyloid Peptide Phagocytosis and Clearance via Vanilloid Family Type 2 Channel Activation Yang, Shaobin Du, Yaqin Zhao, Xiaoqian Tang, Qi Su, Wei Hu, Yuemeng Yu, Peng Int J Mol Sci Article Alzheimer’s disease (AD) is associated with the accumulation and aggregation of amyloid in the brain. The cation channel TRPV2 may mediate the pathological changes in mild cognitive impairment. A high-affinity agonist of TRPV2 named cannabidiol is one of the candidate drugs for AD. However, the molecular mechanism of cannabidiol via TRPV2 in AD remains unknown. The present study investigated whether cannabidiol enhances the phagocytosis and clearance of microglial Aβ via the TRPV2 channel. We used a human dataset, mouse primary neuron and microglia cultures, and AD model mice to evaluate TRPV2 expression and the ability of microglial amyloid-β phagocytosis in vivo and in vitro. The results revealed that TRPV2 expression was reduced in the cortex and hippocampus of AD model mice and AD patients. Cannabidiol enhanced microglial amyloid-β phagocytosis through TRPV2 activation, which increased the mRNA expression of the phagocytosis-related receptors, but knockdown of TRPV2 or Trem2 rescued the expression. TRPV2-mediated effects were also dependent on PDK1/Akt signaling, a pathway in which autophagy was indispensable. Furthermore, cannabidiol treatment successfully attenuated neuroinflammation while simultaneously improving mitochondrial function and ATP production via TRPV2 activation. Therefore, TRPV2 is proposed as a potential therapeutic target in AD, while CBD is a promising drug candidate for AD. MDPI 2022-05-11 /pmc/articles/PMC9140666/ /pubmed/35628181 http://dx.doi.org/10.3390/ijms23105367 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yang, Shaobin Du, Yaqin Zhao, Xiaoqian Tang, Qi Su, Wei Hu, Yuemeng Yu, Peng Cannabidiol Enhances Microglial Beta-Amyloid Peptide Phagocytosis and Clearance via Vanilloid Family Type 2 Channel Activation |
title | Cannabidiol Enhances Microglial Beta-Amyloid Peptide Phagocytosis and Clearance via Vanilloid Family Type 2 Channel Activation |
title_full | Cannabidiol Enhances Microglial Beta-Amyloid Peptide Phagocytosis and Clearance via Vanilloid Family Type 2 Channel Activation |
title_fullStr | Cannabidiol Enhances Microglial Beta-Amyloid Peptide Phagocytosis and Clearance via Vanilloid Family Type 2 Channel Activation |
title_full_unstemmed | Cannabidiol Enhances Microglial Beta-Amyloid Peptide Phagocytosis and Clearance via Vanilloid Family Type 2 Channel Activation |
title_short | Cannabidiol Enhances Microglial Beta-Amyloid Peptide Phagocytosis and Clearance via Vanilloid Family Type 2 Channel Activation |
title_sort | cannabidiol enhances microglial beta-amyloid peptide phagocytosis and clearance via vanilloid family type 2 channel activation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140666/ https://www.ncbi.nlm.nih.gov/pubmed/35628181 http://dx.doi.org/10.3390/ijms23105367 |
work_keys_str_mv | AT yangshaobin cannabidiolenhancesmicroglialbetaamyloidpeptidephagocytosisandclearanceviavanilloidfamilytype2channelactivation AT duyaqin cannabidiolenhancesmicroglialbetaamyloidpeptidephagocytosisandclearanceviavanilloidfamilytype2channelactivation AT zhaoxiaoqian cannabidiolenhancesmicroglialbetaamyloidpeptidephagocytosisandclearanceviavanilloidfamilytype2channelactivation AT tangqi cannabidiolenhancesmicroglialbetaamyloidpeptidephagocytosisandclearanceviavanilloidfamilytype2channelactivation AT suwei cannabidiolenhancesmicroglialbetaamyloidpeptidephagocytosisandclearanceviavanilloidfamilytype2channelactivation AT huyuemeng cannabidiolenhancesmicroglialbetaamyloidpeptidephagocytosisandclearanceviavanilloidfamilytype2channelactivation AT yupeng cannabidiolenhancesmicroglialbetaamyloidpeptidephagocytosisandclearanceviavanilloidfamilytype2channelactivation |