Martins, Ana CatarinaLima, Illyane SofiaPêgo, Ana CatarinaSá Pereira, InêsMartins, GracelinoKapitão, AntoninoGozzelino, Raffaella2023-05-252023-05-252023-051661-6596PURE: 61536768PURE UUID: 575dfe78-d400-4870-bf0f-f046d67aee73Scopus: 85159309935PubMed: 37175654WOS: 000987583300001http://hdl.handle.net/10362/153174Funding Information: This research was funded by FWO and F.R.S.-FNRS under the Excellence of Science Program (EOS), MODEL-IDI Ref. number 30826052 and CD-INFLADIS Ref. number 40007512. A.C.P. is funded by FCT SFRH/BD/14611/2019. I.S.L was funded by FCT SFRH/BD/114552/2016 and is funded by MODEL-IDI Ref. number 30826052; A.C.M was funded by FCT SFRH/BD/104599/2014; R.G. was funded by FCT IF 01495/2016. Publisher Copyright: © 2023 by the authors.Parkinson’s disease (PD) is a multifactorial neurodegenerative pathology characterized by the progressive loss of dopaminergic neurons in the substantia nigra of the brain. Aging is considered the main risk factor for the development of idiopathic PD. However, immunity and inflammation play a crucial role in the pathogenesis of this disorder. In mice, we showed that pro-inflammatory priming of the brain sensitizes to severe PD development, regardless of animal age. Age-related sub-acute inflammation, as well as the activation of the immune response upon exposure to harmful stimuli, enhances PD manifestations. The severity of PD is influenced by the engagement of host resistance mechanisms against infection based on the removal of iron (Fe) from the circulation. The sequestration of Fe by immune cells prevents pathogens from proliferating. However, it leads to the formation of a Fe-loaded circulating compartment. When entering the brain through a compromised blood-brain barrier, Fe-loaded immune cells contribute to enhancing neuroinflammation and brain Fe overload. Thus, pro-inflammatory priming of the brain exacerbates neuronal damage and represents a risk factor for the development of severe PD symptoms. Further investigations are now required to better understand whether therapeutic interventions inhibiting this phenomenon might protect against PD.3270492engimmunityinfectioniron metabolismneuroinflammationParkinson’s diseaseCatalysisMolecular BiologySpectroscopyComputer Science ApplicationsPhysical and Theoretical ChemistryOrganic ChemistryInorganic Chemistryjournal article10.3390/ijms24097949https://www.scopus.com/pages/publications/85159309935