Ameliorative properties of boronic compounds in in vitro and in vivo models of alzheimer’s disease

Panchanan Maiti, Jayeeta Manna, Zoe N. Burch, Denise B. Flaherty, Joseph D. Larkin, Gary L. Dunbar

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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 N2a cells, we observed that TBSA inhibited Aβ42 aggregation and increased cell survival more effectively than did TPVA. These TBSA-induced benefits were extended to C. elegans 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.

Original languageEnglish
Article number6664
Pages (from-to)1-26
Number of pages26
JournalInternational Journal of Molecular Sciences
Volume21
Issue number18
DOIs
StatePublished - Sep 2 2020

Keywords

  • Alzheimer’s disease
  • Amyloid beta protein
  • Amyloid plaque
  • Boron compound
  • C. elegans
  • Neurodegeneration
  • Neuroinflammation

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