TY - JOUR
T1 - Pro-Inflammatory Priming of the Brain
T2 - The Underlying Cause of Parkinson’s Disease
AU - Martins, Ana Catarina
AU - Lima, Illyane Sofia
AU - Pêgo, Ana Catarina
AU - Sá Pereira, Inês
AU - Martins, Gracelino
AU - Kapitão, Antonino
AU - Gozzelino, Raffaella
N1 - Funding 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.
PY - 2023/5
Y1 - 2023/5
N2 - 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.
AB - 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.
KW - immunity
KW - infection
KW - iron metabolism
KW - neuroinflammation
KW - Parkinson’s disease
UR - http://www.scopus.com/inward/record.url?scp=85159309935&partnerID=8YFLogxK
U2 - 10.3390/ijms24097949
DO - 10.3390/ijms24097949
M3 - Article
C2 - 37175654
AN - SCOPUS:85159309935
SN - 1422-0067
VL - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 9
M1 - 7949
ER -