Oxidative stress and α-synuclein conspire in vulnerable neurons to promote Parkinson's disease progression

Abstract

Patients with Parkinson's disease (PD) show selective degeneration of dopaminergic neurons in the substantia nigra and cholinergic neurons in the dorsal motor nucleus (DMnX), but the drivers of this specific susceptibility are unknown. In this issue of the JCI, Musgrove et al. report on their use of an impressive array of in vivo and ex vivo tools for interrogating DMnX neurons and demonstrate that this population exhibits enhanced sensitivity to oxidative stress. Remarkably, this sensitivity was amplified by the overexpression of α-Synuclein (α-Syn), a pathological protein in PD. They further show that oxidative stress augments cell-cell transfer of α-Syn, which may be an important mechanism underlying the development and progression of PD.