Caveolae, CD109, and endothelial cells as targets for treating Alzheimer's disease
Abstract Reduced functionality of transforming growth factor β (TGF‐β) is a major pathogenetic component of Alzheimer's disease (AD). The reduction is caused by an ≈50% decrease in the AD brain of the TGF‐β receptor, TGFBR, causing a bottleneck effect that reduces the downstream actions of TGF‐...
| Main Author: | |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-01-01
|
| Series: | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/trc2.12066 |
| _version_ | 1819290608270835712 |
|---|---|
| author | Jeffrey Fessel |
| author_facet | Jeffrey Fessel |
| author_sort | Jeffrey Fessel |
| collection | DOAJ |
| description | Abstract Reduced functionality of transforming growth factor β (TGF‐β) is a major pathogenetic component of Alzheimer's disease (AD). The reduction is caused by an ≈50% decrease in the AD brain of the TGF‐β receptor, TGFBR, causing a bottleneck effect that reduces the downstream actions of TGF‐β, which is highly disadvantageous for brain function. Degradation of TGFBR occurs in caveolae with participation by caveolin‐1 (Cav‐1) and CD109. Mechanisms for this are discussed. In the cerebral microcirculation, endothelial cells (which are rich in caveolae) carry CD109 as a surface marker that co‐precipitates with Cav‐1. Atorvastatin reduced Cav‐1 by 75% and, because Cav‐1 and CD109 co‐immunoprecipitate reciprocally, atorvastatin would also reduce the level of CD109. Administration of atorvastatin as a component of combination therapy would diminish the degradation of TGFBR and thereby benefit patients with AD. |
| first_indexed | 2024-12-24T03:25:27Z |
| format | Article |
| id | doaj.art-5eb8fa6b779a4df6a33b73c917592afc |
| institution | Directory Open Access Journal |
| issn | 2352-8737 |
| language | English |
| last_indexed | 2024-12-24T03:25:27Z |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| spelling | doaj.art-5eb8fa6b779a4df6a33b73c917592afc2022-12-21T17:17:22ZengWileyAlzheimer’s & Dementia: Translational Research & Clinical Interventions2352-87372020-01-0161n/an/a10.1002/trc2.12066Caveolae, CD109, and endothelial cells as targets for treating Alzheimer's diseaseJeffrey Fessel0Department of Medicine University of California School of Medicine San Francisco California USAAbstract Reduced functionality of transforming growth factor β (TGF‐β) is a major pathogenetic component of Alzheimer's disease (AD). The reduction is caused by an ≈50% decrease in the AD brain of the TGF‐β receptor, TGFBR, causing a bottleneck effect that reduces the downstream actions of TGF‐β, which is highly disadvantageous for brain function. Degradation of TGFBR occurs in caveolae with participation by caveolin‐1 (Cav‐1) and CD109. Mechanisms for this are discussed. In the cerebral microcirculation, endothelial cells (which are rich in caveolae) carry CD109 as a surface marker that co‐precipitates with Cav‐1. Atorvastatin reduced Cav‐1 by 75% and, because Cav‐1 and CD109 co‐immunoprecipitate reciprocally, atorvastatin would also reduce the level of CD109. Administration of atorvastatin as a component of combination therapy would diminish the degradation of TGFBR and thereby benefit patients with AD.https://doi.org/10.1002/trc2.12066Alzheimer's diseaseatorvastatincaveolaecaveolin‐1CD109TGFBR |
| spellingShingle | Jeffrey Fessel Caveolae, CD109, and endothelial cells as targets for treating Alzheimer's disease Alzheimer’s & Dementia: Translational Research & Clinical Interventions Alzheimer's disease atorvastatin caveolae caveolin‐1 CD109 TGFBR |
| title | Caveolae, CD109, and endothelial cells as targets for treating Alzheimer's disease |
| title_full | Caveolae, CD109, and endothelial cells as targets for treating Alzheimer's disease |
| title_fullStr | Caveolae, CD109, and endothelial cells as targets for treating Alzheimer's disease |
| title_full_unstemmed | Caveolae, CD109, and endothelial cells as targets for treating Alzheimer's disease |
| title_short | Caveolae, CD109, and endothelial cells as targets for treating Alzheimer's disease |
| title_sort | caveolae cd109 and endothelial cells as targets for treating alzheimer s disease |
| topic | Alzheimer's disease atorvastatin caveolae caveolin‐1 CD109 TGFBR |
| url | https://doi.org/10.1002/trc2.12066 |
| work_keys_str_mv | AT jeffreyfessel caveolaecd109andendothelialcellsastargetsfortreatingalzheimersdisease |