Sources and triggers of oxidative damage in neurodegeneration

Neurodegeneration describes a group of more than 300 neurological diseases, characterised by neuronal loss and intra- or extracellular protein depositions, as key neuropathological features. Multiple factors play role in the pathogenesis of these group of disorders: mitochondrial dysfunction, membrane damage, calcium dyshomeostasis, metallostasis, defect clearance and renewal mechanisms, to name a few. All these factors, without exceptions, have in common the involvement of immensely increased generation of free radicals and occurrence of oxidative stress, and as a result - exhaustion of the scavenging potency of the cellular redox defence mechanisms. Besides genetic predisposition and environmental exposure to toxins, the main risk factor for developing neurodegeneration is age. And although the "Free radical theory of ageing" was declared dead, it is undisputable that accumulation of damage occurs with age, especially in systems that are regulated by free radical messengers and those that oppose oxidative stress, protein oxidation and the accuracy in protein synthesis and degradation machinery has difficulties to be maintained. This brief review provides a comprehensive summary on the main sources of free radical damage, occurring in the setting of neurodegeneration.