Ameliorative Properties of Boronic Compounds in In Vitro and In Vivo Models of Alzheimer’s Disease
Alzheimer’s disease (AD) is characterized by amyloid (Aβ) aggregation, hyperphosphorylated tau, neuroinflammation, and severe memory deficits. Reports that certain boronic compounds can reduce amyloid accumulation and neuroinflammation prompted us to compare trans-2-phenyl-vinyl-boronic-acid-MIDA-es...
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/18/6664 |
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| author | Panchanan Maiti Jayeeta Manna Zoe N. Burch Denise B. Flaherty Joseph D. Larkin Gary L. Dunbar |
| author_facet | Panchanan Maiti Jayeeta Manna Zoe N. Burch Denise B. Flaherty Joseph D. Larkin Gary L. Dunbar |
| author_sort | Panchanan Maiti |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is characterized by amyloid (Aβ) aggregation, hyperphosphorylated tau, neuroinflammation, and severe memory deficits. Reports that certain boronic compounds can reduce amyloid accumulation and neuroinflammation prompted us to compare trans-2-phenyl-vinyl-boronic-acid-MIDA-ester (TPVA) and trans-beta-styryl-boronic-acid (TBSA) as treatments of deficits in in vitro and in vivo models of AD. We hypothesized that these compounds would reduce neuropathological deficits in cell-culture and animal models of AD. Using a dot-blot assay and cultured N<sub>2</sub>a cells, we observed that TBSA inhibited Aβ42 aggregation and increased cell survival more effectively than did TPVA. These TBSA-induced benefits were extended to <i>C. elegans</i> expressing Aβ42 and to the 5xFAD mouse model of AD. Oral administration of 0.5 mg/kg dose of TBSA or an equivalent amount of methylcellulose vehicle to groups of six- and 12-month-old 5xFAD or wild-type mice over a two-month period prevented recognition- and spatial-memory deficits in the novel-object recognition and Morris-water-maze memory tasks, respectively, and reduced the number of pyknotic and degenerated cells, Aβ plaques, and GFAP and Iba-1 immunoreactivity in the hippocampus and cortex of these mice. These findings indicate that TBSA exerts neuroprotective properties by decreasing amyloid plaque burden and neuroinflammation, thereby preventing neuronal death and preserving memory function in the 5xFAD mice. |
| first_indexed | 2024-03-10T16:23:44Z |
| format | Article |
| id | doaj.art-9830c73f139d40abb234dead2dd2a38b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:23:44Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9830c73f139d40abb234dead2dd2a38b2023-11-20T13:26:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012118666410.3390/ijms21186664Ameliorative Properties of Boronic Compounds in In Vitro and In Vivo Models of Alzheimer’s DiseasePanchanan Maiti0Jayeeta Manna1Zoe N. Burch2Denise B. Flaherty3Joseph D. Larkin4Gary L. Dunbar5Field Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mt. Pleasant, MI 48859, USAField Neurosciences Institute, Ascension St. Mary, Saginaw, MI 48604, USADepartment of Biology, Eckerd College, St. Petersburg, FL 33711, USADepartment of Biology, Eckerd College, St. Petersburg, FL 33711, USADepartment of Chemistry, Eckerd College, St. Petersburg, FL 33711, USAField Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mt. Pleasant, MI 48859, USAAlzheimer’s disease (AD) is characterized by amyloid (Aβ) aggregation, hyperphosphorylated tau, neuroinflammation, and severe memory deficits. Reports that certain boronic compounds can reduce amyloid accumulation and neuroinflammation prompted us to compare trans-2-phenyl-vinyl-boronic-acid-MIDA-ester (TPVA) and trans-beta-styryl-boronic-acid (TBSA) as treatments of deficits in in vitro and in vivo models of AD. We hypothesized that these compounds would reduce neuropathological deficits in cell-culture and animal models of AD. Using a dot-blot assay and cultured N<sub>2</sub>a cells, we observed that TBSA inhibited Aβ42 aggregation and increased cell survival more effectively than did TPVA. These TBSA-induced benefits were extended to <i>C. elegans</i> expressing Aβ42 and to the 5xFAD mouse model of AD. Oral administration of 0.5 mg/kg dose of TBSA or an equivalent amount of methylcellulose vehicle to groups of six- and 12-month-old 5xFAD or wild-type mice over a two-month period prevented recognition- and spatial-memory deficits in the novel-object recognition and Morris-water-maze memory tasks, respectively, and reduced the number of pyknotic and degenerated cells, Aβ plaques, and GFAP and Iba-1 immunoreactivity in the hippocampus and cortex of these mice. These findings indicate that TBSA exerts neuroprotective properties by decreasing amyloid plaque burden and neuroinflammation, thereby preventing neuronal death and preserving memory function in the 5xFAD mice.https://www.mdpi.com/1422-0067/21/18/6664Alzheimer’s diseaseamyloid beta proteinneurodegenerationboron compoundneuroinflammationamyloid plaque |
| spellingShingle | Panchanan Maiti Jayeeta Manna Zoe N. Burch Denise B. Flaherty Joseph D. Larkin Gary L. Dunbar Ameliorative Properties of Boronic Compounds in In Vitro and In Vivo Models of Alzheimer’s Disease International Journal of Molecular Sciences Alzheimer’s disease amyloid beta protein neurodegeneration boron compound neuroinflammation amyloid plaque |
| title | Ameliorative Properties of Boronic Compounds in In Vitro and In Vivo Models of Alzheimer’s Disease |
| title_full | Ameliorative Properties of Boronic Compounds in In Vitro and In Vivo Models of Alzheimer’s Disease |
| title_fullStr | Ameliorative Properties of Boronic Compounds in In Vitro and In Vivo Models of Alzheimer’s Disease |
| title_full_unstemmed | Ameliorative Properties of Boronic Compounds in In Vitro and In Vivo Models of Alzheimer’s Disease |
| title_short | Ameliorative Properties of Boronic Compounds in In Vitro and In Vivo Models of Alzheimer’s Disease |
| title_sort | ameliorative properties of boronic compounds in in vitro and in vivo models of alzheimer s disease |
| topic | Alzheimer’s disease amyloid beta protein neurodegeneration boron compound neuroinflammation amyloid plaque |
| url | https://www.mdpi.com/1422-0067/21/18/6664 |
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