Glia and Alzheimer’s disease: the pharmacological manipulation as promising tool against pathology progression

Alzheimer’s disease (AD) exerts an increasingly serious health and economic burden. Current treatments provide inadequate symptomatic relief as several distinct pathological processes are thought to underlie the decline of cognitive and neural function seen in AD. Neurological disorders can be considered as failures of nervous system homeostasis in response to environmental, systemic, or endogenous factors. Glial cells, being the central element of brain homeostasis, are ultimately involved in the pathogenesis of several neurological disorders, including AD. For this reason, the pharmacological manipulation of glia functionality can be considered a promising therapeutic approach. In this context, we have demonstrated, by using different preclinical models of AD, the therapeutic potential of palmitoylethanolamide (PEA), an endogenous lipid compound endowed of several pharmacological properties. Our data demonstrate that PEA reduces Aβ formation, the phosphorylation of tau proteins and promotes neuronal survival, as well as it improves learning and memory. Finally, we have demonstrated that PEA normalizes glial functions and restrains neuroinflammation. Since PEA is already licenced for use in humans, displaying a high tolerability and a safety profile, it would be an ideal candidate for a long-term use lasting several years, as potential AD treatment requires.