Leptinhas been found to reduce the levels of toxic extracellularamyloidbeta (Aβ) and induce protective functions in a range of neurodegenerative models 14.Amyloidprecursorprotein(APP) is a type 1 transmembrane glycoprotein with a central role in AD, and neuronal homeostasis 25 - 27.
Low plasma levels ofleptin, an adipocyte hormone acting on the hypothalamus to regulate body weight, have also been correlated with increased AD risk. Therefore, increasedamyloid-beta levels derived fromamyloidprecursorprotein(APP) may disrupt hypothalamicleptinsignaling early in AD.
This particular example perfectly highlights why Protein Amyloid Precursor Leptin is so captivating.
We previously found that the levels of solubleamyloidprecursorproteinα (sAPPα) are partly regulated by acetylcholinesterase (AChE) in human non-small cell lung cancer cell lines A549 (p53 wild-type) and H1299 (p53-null). In this study, we hypothesize that sAPPα is partly regulated byleptin, a hormone classically recognized for its anorexigenic role in appetite regulation— yet ...
This particular example perfectly highlights why Protein Amyloid Precursor Leptin is so captivating.
While many factors likely contribute to AD progression, it is widely accepted that AD is driven by the accumulation of β-amyloid(Aβ), a small, fibrillogenic peptide generated by the sequential proteolysis of theamyloidprecursorproteinby the β- and γ-secretases.
Furthermore, our data shows thatleptinreduces the NF-κB-mediated transcription of BACE1 and consequently reducesAmyloid-β genesis. Our study provides a valuable insight and a novel mechanism by whichleptinreduces BACE1 expression andAmyloid-β production and may help design potential therapeutic interventions.
