Nicotinic receptor components of amyloid beta 42 proteome regulation in human neural cells

Alzheimer’s disease (AD) is associated with chronic neurodegeneration often accompanied by elevated levels of the neurotoxic peptide amyloid-beta 1–42 (Aβ(42)) in the brain. Studies show that extracellular Aβ(42) binds to various cell surface receptors including the human α7 nicotinic acetylcholine receptor (nAChR) and activates pathways of neurotoxicity leading to cell death. The α7 nAChR is thus considered a promising drug target for therapy against neurodegenerative disease such as AD. In this study, we use mass spectrometry-based label-free precursor ion quantification to identify proteins and pathways that are changed by a 72-hour treatment with Aβ(42) or Aβ(42) in the presence of the α7 nAChR blocker, α-bungarotoxin (Bgtx) in the human neuroblastoma SH-SY5Y cell line. Bioinformatic gene ontology enrichment analysis was used to identify and characterize proteins and pathways altered by Aβ(42) presentation. The results support evidence on the involvement of mitochondrial proteins in Aβ(42) responses and define potential mechanisms of α7 nAChR mediated amyloid toxicity. These findings can inform pharmacological strategies for drug design and treatment against amyloid disease.