Neuronal ApoE Regulates the Cell-to-Cell Transmission of α-Synuclein
The presence of protein inclusions, called Lewy bodies (LBs) and Lewy neurites (LNs), in the brain is the main feature of Parkinson’s disease (PD). Recent evidence that the prion-like propagation of α-synuclein (α-syn), as a major component of LBs and LNs, plays an important role in the progression...
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MDPI AG
2022-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/15/8311 |
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| author | Seo-Jun Kang Soo-Jeong Kim Hye Rin Noh Beom Jin Kim Jae-Bong Kim Uram Jin Sun Ah Park Sang Myun Park |
| author_facet | Seo-Jun Kang Soo-Jeong Kim Hye Rin Noh Beom Jin Kim Jae-Bong Kim Uram Jin Sun Ah Park Sang Myun Park |
| author_sort | Seo-Jun Kang |
| collection | DOAJ |
| description | The presence of protein inclusions, called Lewy bodies (LBs) and Lewy neurites (LNs), in the brain is the main feature of Parkinson’s disease (PD). Recent evidence that the prion-like propagation of α-synuclein (α-syn), as a major component of LBs and LNs, plays an important role in the progression of PD has gained much attention, although the molecular mechanism remains unclear. In this study, we evaluated whether neuronal ApoE regulates the cell-to-cell transmission of α-syn and explored its molecular mechanism using in vitro and in vivo model systems. We demonstrate that neuronal ApoE deficiency attenuates both α-syn uptake and release by downregulating LRP-1 and LDLR expression and enhancing chaperone-mediated autophagy activity, respectively, thereby contributing to α-syn propagation. In addition, we observed that α-syn propagation was attenuated in ApoE knockout mice injected with pre-formed mouse α-syn fibrils. This study will help our understanding of the molecular mechanisms underlying α-syn propagation. |
| first_indexed | 2024-03-09T05:22:36Z |
| format | Article |
| id | doaj.art-d1e3f4411b62429eab30281d933eb78b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:22:36Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d1e3f4411b62429eab30281d933eb78b2023-12-03T12:39:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012315831110.3390/ijms23158311Neuronal ApoE Regulates the Cell-to-Cell Transmission of α-SynucleinSeo-Jun Kang0Soo-Jeong Kim1Hye Rin Noh2Beom Jin Kim3Jae-Bong Kim4Uram Jin5Sun Ah Park6Sang Myun Park7Department of Pharmacology, Ajou University School of Medicine, Suwon 16499, KoreaCenter for Convergence Research of Neurological Disorders, Ajou University School of Medicine, Suwon 16499, KoreaDepartment of Pharmacology, Ajou University School of Medicine, Suwon 16499, KoreaDepartment of Pharmacology, Ajou University School of Medicine, Suwon 16499, KoreaDepartment of Pharmacology, Ajou University School of Medicine, Suwon 16499, KoreaDepartment of Pharmacology, Ajou University School of Medicine, Suwon 16499, KoreaCenter for Convergence Research of Neurological Disorders, Ajou University School of Medicine, Suwon 16499, KoreaDepartment of Pharmacology, Ajou University School of Medicine, Suwon 16499, KoreaThe presence of protein inclusions, called Lewy bodies (LBs) and Lewy neurites (LNs), in the brain is the main feature of Parkinson’s disease (PD). Recent evidence that the prion-like propagation of α-synuclein (α-syn), as a major component of LBs and LNs, plays an important role in the progression of PD has gained much attention, although the molecular mechanism remains unclear. In this study, we evaluated whether neuronal ApoE regulates the cell-to-cell transmission of α-syn and explored its molecular mechanism using in vitro and in vivo model systems. We demonstrate that neuronal ApoE deficiency attenuates both α-syn uptake and release by downregulating LRP-1 and LDLR expression and enhancing chaperone-mediated autophagy activity, respectively, thereby contributing to α-syn propagation. In addition, we observed that α-syn propagation was attenuated in ApoE knockout mice injected with pre-formed mouse α-syn fibrils. This study will help our understanding of the molecular mechanisms underlying α-syn propagation.https://www.mdpi.com/1422-0067/23/15/8311Parkinson’s diseaseLewy bodyα-synuclein propagationα-synuclein uptakeα-synuclein releaseApoE |
| spellingShingle | Seo-Jun Kang Soo-Jeong Kim Hye Rin Noh Beom Jin Kim Jae-Bong Kim Uram Jin Sun Ah Park Sang Myun Park Neuronal ApoE Regulates the Cell-to-Cell Transmission of α-Synuclein International Journal of Molecular Sciences Parkinson’s disease Lewy body α-synuclein propagation α-synuclein uptake α-synuclein release ApoE |
| title | Neuronal ApoE Regulates the Cell-to-Cell Transmission of α-Synuclein |
| title_full | Neuronal ApoE Regulates the Cell-to-Cell Transmission of α-Synuclein |
| title_fullStr | Neuronal ApoE Regulates the Cell-to-Cell Transmission of α-Synuclein |
| title_full_unstemmed | Neuronal ApoE Regulates the Cell-to-Cell Transmission of α-Synuclein |
| title_short | Neuronal ApoE Regulates the Cell-to-Cell Transmission of α-Synuclein |
| title_sort | neuronal apoe regulates the cell to cell transmission of α synuclein |
| topic | Parkinson’s disease Lewy body α-synuclein propagation α-synuclein uptake α-synuclein release ApoE |
| url | https://www.mdpi.com/1422-0067/23/15/8311 |
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