A Pyridazine-Based Fluorescent Probe Targeting Aβ Plaques in Alzheimer’s Disease
Accumulation of β-amyloid (Aβ) plaques comprising Aβ40 and Aβ42 in the brain is the most significant factor in the pathogenesis of Alzheimer’s disease (AD). Thus, the detection of Aβ plaques has increasingly attracted interest in the context of AD diagnosis. In the present study, a fluorescent pyrid...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Journal of Analytical Methods in Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2018/1651989 |
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| author | Yong Dae Park Jeum-Jong Kim Sungbeom Lee Chul-Hong Park Hyoung-Woo Bai Seung Sik Lee |
| author_facet | Yong Dae Park Jeum-Jong Kim Sungbeom Lee Chul-Hong Park Hyoung-Woo Bai Seung Sik Lee |
| author_sort | Yong Dae Park |
| collection | DOAJ |
| description | Accumulation of β-amyloid (Aβ) plaques comprising Aβ40 and Aβ42 in the brain is the most significant factor in the pathogenesis of Alzheimer’s disease (AD). Thus, the detection of Aβ plaques has increasingly attracted interest in the context of AD diagnosis. In the present study, a fluorescent pyridazine-based dye that can detect and image Aβ plaques was designed and synthesized, and its optical properties in the presence of Aβ aggregates were evaluated. An approximately 34-fold increase in emission intensity was exhibited by the fluorescent probe after binding with Aβ aggregates, for which it showed high affinity (KD = 0.35 µM). Moreover, the reasonable hydrophobic properties of the probe (log P = 2.94) allow it to penetrate the blood brain barrier (BBB). In addition, the pyridazine-based probe was used in the histological costaining of transgenic mouse (APP/PS1) brain sections to validate the selective binding of the probe to Aβ plaques. The results suggest that the pyridazine-based compound has the potential to serve as a fluorescent probe for the diagnosis of AD. |
| format | Article |
| id | doaj-art-080622b182974254907ea5df15f57595 |
| institution | Kabale University |
| issn | 2090-8865 2090-8873 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Analytical Methods in Chemistry |
| spelling | doaj-art-080622b182974254907ea5df15f575952025-08-20T03:55:27ZengWileyJournal of Analytical Methods in Chemistry2090-88652090-88732018-01-01201810.1155/2018/16519891651989A Pyridazine-Based Fluorescent Probe Targeting Aβ Plaques in Alzheimer’s DiseaseYong Dae Park0Jeum-Jong Kim1Sungbeom Lee2Chul-Hong Park3Hyoung-Woo Bai4Seung Sik Lee5Research Division for Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Republic of KoreaTechnology Innovation Support Team, Korea Research Institute of Chemical Technology (KRICT), Deajeon 305-600, Republic of KoreaResearch Division for Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Republic of KoreaResearch Division for Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Republic of KoreaResearch Division for Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Republic of KoreaResearch Division for Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Republic of KoreaAccumulation of β-amyloid (Aβ) plaques comprising Aβ40 and Aβ42 in the brain is the most significant factor in the pathogenesis of Alzheimer’s disease (AD). Thus, the detection of Aβ plaques has increasingly attracted interest in the context of AD diagnosis. In the present study, a fluorescent pyridazine-based dye that can detect and image Aβ plaques was designed and synthesized, and its optical properties in the presence of Aβ aggregates were evaluated. An approximately 34-fold increase in emission intensity was exhibited by the fluorescent probe after binding with Aβ aggregates, for which it showed high affinity (KD = 0.35 µM). Moreover, the reasonable hydrophobic properties of the probe (log P = 2.94) allow it to penetrate the blood brain barrier (BBB). In addition, the pyridazine-based probe was used in the histological costaining of transgenic mouse (APP/PS1) brain sections to validate the selective binding of the probe to Aβ plaques. The results suggest that the pyridazine-based compound has the potential to serve as a fluorescent probe for the diagnosis of AD.http://dx.doi.org/10.1155/2018/1651989 |
| spellingShingle | Yong Dae Park Jeum-Jong Kim Sungbeom Lee Chul-Hong Park Hyoung-Woo Bai Seung Sik Lee A Pyridazine-Based Fluorescent Probe Targeting Aβ Plaques in Alzheimer’s Disease Journal of Analytical Methods in Chemistry |
| title | A Pyridazine-Based Fluorescent Probe Targeting Aβ Plaques in Alzheimer’s Disease |
| title_full | A Pyridazine-Based Fluorescent Probe Targeting Aβ Plaques in Alzheimer’s Disease |
| title_fullStr | A Pyridazine-Based Fluorescent Probe Targeting Aβ Plaques in Alzheimer’s Disease |
| title_full_unstemmed | A Pyridazine-Based Fluorescent Probe Targeting Aβ Plaques in Alzheimer’s Disease |
| title_short | A Pyridazine-Based Fluorescent Probe Targeting Aβ Plaques in Alzheimer’s Disease |
| title_sort | pyridazine based fluorescent probe targeting aβ plaques in alzheimer s disease |
| url | http://dx.doi.org/10.1155/2018/1651989 |
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