Neurodegenerative diseases encompass complex cell signaling disturbances that initially damage neuronal circuits and synapses. Due to multiple protective mechanisms enacted to counteract the onset of neurodegenerative diseases, there is often a prolonged period without noticeable impairments during their initiation. Since severe cognitive deficit or vision loss takes place after that period there is an opportunity to harness endogenous protective mechanisms as potential therapeutic approaches. The activation of the biosynthesis of the docosanoid mediator neuroprotectin D1 (NPD1) is an early response to the upsurge of protein misfolding and other neuroinflammatory events. This overview discusses the potent neuroprotective and inflammation-modulating bioactivity of NPD1. This lipid mediator represents an early response to neurodegenerations, aiming to restore homeostasis.