Association of Kisspeptin and α-Synuclein in Cholinergic Neurons

Dementia with Lewy bodies reflects the etiopathological convergence between amyloid-β (Aβ) deposits and α-synuclein (α-syn)-laden inclusions in cholinergic neurons. The recent revelation that kisspeptin-10 (KP-10), which is arbitrated by its G protein-coupled receptor, GPR54, is predisposed to alleviating Aβ toxicity via an extracellular binding mechanism heralds a new horizon for α-syn-based treatments. Given the structural similarities between α-syn’s non-amyloid-β component (NAC) and Aβ’s C-terminus, we postulated that KP-10 would augment cholinergic resistance against α-syn’s noxious insults through preferential binding. Herein, our findings insinuate a mechanistic link between KP-10 and α-syn pathology, which may have broader connotations for α-syn-centric drug design endeavors.