sq-23377 and sulforaphane

Mer tyrosine kinase (MerTK) activity necessary for amyloid-stimulated phagocytosis strongly implicates that MerTK dysregulation might contribute to chronic inflammation implicated in Alzheimer's disease (AD) pathology. However, the precise mechanism involved in the regulation of MerTK expression by amyloid-β (Aβ) in proinflammatory environment has not yet been ascertained.. The objective of this study was to determine the underlying mechanism involved in Aβ-mediated decrease in MerTK expression through Aβ-mediated regulation of MerTK expression and its modulation by sulforaphane in human THP-1 macrophages challenged with Aβ1-42. We used protein preparation, Ca. Aβ1-42 elicited a marked decrease in MerTK expression along with increased intracellular Ca. These findings implicate that targeting of MerTK with phytochemical sulforaphane as a mechanism for preventing Aβ1-42-induced neuroinflammation has potential to be applied in AD therapeutics.

Topics: Amyloid beta-Peptides; Anti-Inflammatory Agents; Antibodies; c-Mer Tyrosine Kinase; Calcium; Calcium Ionophores; Cell Fractionation; Cycloheximide; Gene Expression Regulation; Humans; Interleukin-1beta; Ionomycin; Isothiocyanates; Nitriles; Peptide Fragments; Protein Synthesis Inhibitors; RNA, Small Interfering; Signal Transduction; Sulfones; Sulfoxides; Thapsigargin; THP-1 Cells; Tumor Necrosis Factor-alpha