Aβ Oligomer Toxicity-Reducing Therapy for the Prevention of Alzheimer’s Disease: Importance of the Nrf2 and PPARγ Pathways
Recent studies have revealed that soluble amyloid-β oligomers (AβOs) play a pathogenetic role in Alzheimer’s disease (AD). Indeed, AβOs induce neurotoxic and synaptotoxic effects and are also critically involved in neuroinflammation. Oxidative stress appears to be a crucial event underlying these pa...
| Main Author: | |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/12/10/1386 |
| _version_ | 1797600633687113728 |
|---|---|
| author | Wataru Araki |
| author_facet | Wataru Araki |
| author_sort | Wataru Araki |
| collection | DOAJ |
| description | Recent studies have revealed that soluble amyloid-β oligomers (AβOs) play a pathogenetic role in Alzheimer’s disease (AD). Indeed, AβOs induce neurotoxic and synaptotoxic effects and are also critically involved in neuroinflammation. Oxidative stress appears to be a crucial event underlying these pathological effects of AβOs. From a therapeutic standpoint, new drugs for AD designed to remove AβOs or inhibit the formation of AβOs are currently being developed. However, it is also worth considering strategies for preventing AβO toxicity itself. In particular, small molecules with AβO toxicity-reducing activity have potential as drug candidates. Among such small molecules, those that can enhance Nrf2 and/or PPARγ activity can effectively inhibit AβO toxicity. In this review, I summarize studies on the small molecules that counteract AβO toxicity and are capable of activating Nrf2 and/or PPARγ. I also discuss how these interrelated pathways are involved in the mechanisms by which these small molecules prevent AβO-induced neurotoxicity and neuroinflammation. I propose that AβO toxicity-reducing therapy, designated ATR-T, could be a beneficial, complementary strategy for the prevention and treatment of AD. |
| first_indexed | 2024-03-11T03:51:36Z |
| format | Article |
| id | doaj.art-4f1cd2cdbea84751a7a79ef1fb8e6730 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T03:51:36Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-4f1cd2cdbea84751a7a79ef1fb8e67302023-11-18T00:52:51ZengMDPI AGCells2073-44092023-05-011210138610.3390/cells12101386Aβ Oligomer Toxicity-Reducing Therapy for the Prevention of Alzheimer’s Disease: Importance of the Nrf2 and PPARγ PathwaysWataru Araki0Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, JapanRecent studies have revealed that soluble amyloid-β oligomers (AβOs) play a pathogenetic role in Alzheimer’s disease (AD). Indeed, AβOs induce neurotoxic and synaptotoxic effects and are also critically involved in neuroinflammation. Oxidative stress appears to be a crucial event underlying these pathological effects of AβOs. From a therapeutic standpoint, new drugs for AD designed to remove AβOs or inhibit the formation of AβOs are currently being developed. However, it is also worth considering strategies for preventing AβO toxicity itself. In particular, small molecules with AβO toxicity-reducing activity have potential as drug candidates. Among such small molecules, those that can enhance Nrf2 and/or PPARγ activity can effectively inhibit AβO toxicity. In this review, I summarize studies on the small molecules that counteract AβO toxicity and are capable of activating Nrf2 and/or PPARγ. I also discuss how these interrelated pathways are involved in the mechanisms by which these small molecules prevent AβO-induced neurotoxicity and neuroinflammation. I propose that AβO toxicity-reducing therapy, designated ATR-T, could be a beneficial, complementary strategy for the prevention and treatment of AD.https://www.mdpi.com/2073-4409/12/10/1386Alzheimer’s diseaseamyloid betaneuroinflammationNrf2oligomerPPARγ |
| spellingShingle | Wataru Araki Aβ Oligomer Toxicity-Reducing Therapy for the Prevention of Alzheimer’s Disease: Importance of the Nrf2 and PPARγ Pathways Cells Alzheimer’s disease amyloid beta neuroinflammation Nrf2 oligomer PPARγ |
| title | Aβ Oligomer Toxicity-Reducing Therapy for the Prevention of Alzheimer’s Disease: Importance of the Nrf2 and PPARγ Pathways |
| title_full | Aβ Oligomer Toxicity-Reducing Therapy for the Prevention of Alzheimer’s Disease: Importance of the Nrf2 and PPARγ Pathways |
| title_fullStr | Aβ Oligomer Toxicity-Reducing Therapy for the Prevention of Alzheimer’s Disease: Importance of the Nrf2 and PPARγ Pathways |
| title_full_unstemmed | Aβ Oligomer Toxicity-Reducing Therapy for the Prevention of Alzheimer’s Disease: Importance of the Nrf2 and PPARγ Pathways |
| title_short | Aβ Oligomer Toxicity-Reducing Therapy for the Prevention of Alzheimer’s Disease: Importance of the Nrf2 and PPARγ Pathways |
| title_sort | aβ oligomer toxicity reducing therapy for the prevention of alzheimer s disease importance of the nrf2 and pparγ pathways |
| topic | Alzheimer’s disease amyloid beta neuroinflammation Nrf2 oligomer PPARγ |
| url | https://www.mdpi.com/2073-4409/12/10/1386 |
| work_keys_str_mv | AT wataruaraki aboligomertoxicityreducingtherapyforthepreventionofalzheimersdiseaseimportanceofthenrf2andppargpathways |