Astemizole, a Second-Generation Histamine H1-Receptor Antagonist, Did Not Attenuate the Aggregation Process of α-Synuclein In Vitro
The antihistamine astemizole has shown disease-modifying effects in several preclinical disease models of Parkinson’s disease (PD). Astemizole also interacts with an anomalous aggregation of Alzheimer’s disease-related amyloid-β (Aβ) peptide and has inhibitory activity on the human prion protein PrP...
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MDPI AG
2024-03-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/12/3/611 |
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| author | Jung Il Choi Hyunjo Lee Dong Jun Kim Eun Suk Park Kyung Yeon Lee Hui-Jun Yang |
| author_facet | Jung Il Choi Hyunjo Lee Dong Jun Kim Eun Suk Park Kyung Yeon Lee Hui-Jun Yang |
| author_sort | Jung Il Choi |
| collection | DOAJ |
| description | The antihistamine astemizole has shown disease-modifying effects in several preclinical disease models of Parkinson’s disease (PD). Astemizole also interacts with an anomalous aggregation of Alzheimer’s disease-related amyloid-β (Aβ) peptide and has inhibitory activity on the human prion protein PrP<sup>Sc</sup>. We hypothesized that the proposed preclinical benefits of astemizole on PD can be associated with the attenuation of pathological α-synuclein (α-syn) aggregation. We tested the effects of astemizole on the fibrillation processes of amyloid peptides using thioflavin T aggregation monitoring, Congo red spectral analysis, cell viability study, and transmission electron microscopic imaging. We found that astemizole did not inhibit α-syn aggregation in vitro even at a high molar ratio but inhibited the assembly of Aβ aggregates. Our results suggest that the inhibitory effect of astemizole on amyloid formation is target-protein selective, and the proposed beneficial effects of this compound observed in translational PD models might not be due to its ameliorating effects on α-syn aggregation. |
| first_indexed | 2024-04-24T18:31:36Z |
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| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-04-24T18:31:36Z |
| publishDate | 2024-03-01 |
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| spelling | doaj.art-c4a3239028824121859b28dc88f436062024-03-27T13:22:56ZengMDPI AGBiomedicines2227-90592024-03-0112361110.3390/biomedicines12030611Astemizole, a Second-Generation Histamine H1-Receptor Antagonist, Did Not Attenuate the Aggregation Process of α-Synuclein In VitroJung Il Choi0Hyunjo Lee1Dong Jun Kim2Eun Suk Park3Kyung Yeon Lee4Hui-Jun Yang5Basic-Clinical Convergence Research Institute, University of Ulsan, Ulsan 44033, Republic of KoreaDepartment of Neurology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Republic of KoreaBasic-Clinical Convergence Research Institute, University of Ulsan, Ulsan 44033, Republic of KoreaDepartment of Neurosurgery, Wonkwang University Hospital, Wonkwang University School of Medicine, Iksan 54538, Republic of KoreaDepartment of Pediatrics, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Republic of KoreaBasic-Clinical Convergence Research Institute, University of Ulsan, Ulsan 44033, Republic of KoreaThe antihistamine astemizole has shown disease-modifying effects in several preclinical disease models of Parkinson’s disease (PD). Astemizole also interacts with an anomalous aggregation of Alzheimer’s disease-related amyloid-β (Aβ) peptide and has inhibitory activity on the human prion protein PrP<sup>Sc</sup>. We hypothesized that the proposed preclinical benefits of astemizole on PD can be associated with the attenuation of pathological α-synuclein (α-syn) aggregation. We tested the effects of astemizole on the fibrillation processes of amyloid peptides using thioflavin T aggregation monitoring, Congo red spectral analysis, cell viability study, and transmission electron microscopic imaging. We found that astemizole did not inhibit α-syn aggregation in vitro even at a high molar ratio but inhibited the assembly of Aβ aggregates. Our results suggest that the inhibitory effect of astemizole on amyloid formation is target-protein selective, and the proposed beneficial effects of this compound observed in translational PD models might not be due to its ameliorating effects on α-syn aggregation.https://www.mdpi.com/2227-9059/12/3/611astemizolesynucleinamyloidParkinson’s disease |
| spellingShingle | Jung Il Choi Hyunjo Lee Dong Jun Kim Eun Suk Park Kyung Yeon Lee Hui-Jun Yang Astemizole, a Second-Generation Histamine H1-Receptor Antagonist, Did Not Attenuate the Aggregation Process of α-Synuclein In Vitro Biomedicines astemizole synuclein amyloid Parkinson’s disease |
| title | Astemizole, a Second-Generation Histamine H1-Receptor Antagonist, Did Not Attenuate the Aggregation Process of α-Synuclein In Vitro |
| title_full | Astemizole, a Second-Generation Histamine H1-Receptor Antagonist, Did Not Attenuate the Aggregation Process of α-Synuclein In Vitro |
| title_fullStr | Astemizole, a Second-Generation Histamine H1-Receptor Antagonist, Did Not Attenuate the Aggregation Process of α-Synuclein In Vitro |
| title_full_unstemmed | Astemizole, a Second-Generation Histamine H1-Receptor Antagonist, Did Not Attenuate the Aggregation Process of α-Synuclein In Vitro |
| title_short | Astemizole, a Second-Generation Histamine H1-Receptor Antagonist, Did Not Attenuate the Aggregation Process of α-Synuclein In Vitro |
| title_sort | astemizole a second generation histamine h1 receptor antagonist did not attenuate the aggregation process of α synuclein in vitro |
| topic | astemizole synuclein amyloid Parkinson’s disease |
| url | https://www.mdpi.com/2227-9059/12/3/611 |
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