“…Low-level oxidative stress is a by-product of normal metabolic activity (Sohal and Orr, 2011), which, in a healthy cell, is minimized through rate-limited metabolism and further curtailed by endogenous anti-oxidants (Halliwell, 1992; Mills et al, 2010). Accumulation of unbound non-heme iron upsets that equilibrium and accelerates the rate of oxidative stress that enhances degradation of macromolecular cell components, perforates cell and mitochondrial membranes, impedes mitochondrial activity, promotes DNA mutations, and accelerates the rate of apoptosis (Halliwell, 1992; Mills et al, 2010; Hare et al, 2013; Ward et al, 2014; Granold et al, 2015). Through a separate but related mechanism, iron-catalyzed oxidative stress also increases pro-inflammatory cytokines, initiating the propagating cycle of neuroinflammation (Williams et al, 2012) that has been implicated in neurodegeneration (Xu et al, 2012; see Ward et al, 2014 for a review).…”