Ameliorative Properties of Boronic Compounds in In Vitro and In Vivo Models of Alzheimer's Disease

• Published in: International journal of molecular sciences 2020-09, Vol.21 (18), p.6664
• Main Authors: Maiti, Panchanan, Manna, Jayeeta, Burch, Zoe N, Flaherty, Denise B, Larkin, Joseph D, Dunbar, Gary L
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer's disease; amyloid beta protein; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - metabolism; amyloid plaque; Animal models; Animals; Boron; boron compound; Boronic Acids - pharmacology; Caenorhabditis elegans - drug effects; Caenorhabditis elegans - metabolism; Cell culture; Cell Line, Tumor; Cognition & reasoning; Cognitive ability; Disease; Disease Models, Animal; FDA approval; Female; Glial fibrillary acidic protein; Hippocampus - drug effects; Hippocampus - metabolism; Immunoreactivity; Inflammation; Male; Medical research; Memory; Memory Disorders - drug therapy; Memory Disorders - metabolism; Memory tasks; Mice; Mice, Transgenic; Neurodegeneration; neuroinflammation; Neuroprotection; Neuroprotective Agents - pharmacology; Neurotoxicity; Oral administration; Pattern recognition; Plaque, Amyloid - metabolism; Plaques; Researchers; Spatial analysis; Spatial memory; Spatial Memory - drug effects; Sulfonium Compounds - pharmacology; Tau protein
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21186664

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 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 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.