Perspective
Mitochondrial signaling on innate immunity activation in Parkinson disease

https://doi.org/10.1016/j.conb.2022.102664Get rights and content
Under a Creative Commons license
open access

Highlights

  • Extensive mitochondrial fragmentation allows the exposure of DAMPs.

  • Chronic TLR signaling promotes exacerbated neuronal innate immune response.

  • α-synuclein overexpression may be a consequence of neuronal innate immunity activation.

  • α-synuclein targets the mitochondria and induces its dysfunction.

  • Damaged mitochondria and α-synuclein aggregates can be released and signal glial cells.

Abstract

Parkinson's disease (PD) is a neurodegenerative disease characterized by the accumulation of alpha-synuclein (aSyn) in the nigrostriatal pathway that is followed by severe neuroinflammatory response. PD etiology is still puzzling; however, the mitocentric view might explain the vast majority of molecular findings not only in the brain, but also at systemic level. While neuronal degeneration is tightly associated with mitochondrial dysfunction, the causal role between aSyn accumulation and mitochondrial dysfunction still requires further investigation. Moreover, mitochondrial dysfunction can elicit an inflammatory response that may be transmitted locally but also in a long range through systemic circulation. Furthermore, mitochondrial-driven innate immune activation may involve the synthesis of antimicrobial peptides, of which aSyn poses as a good candidate. While there is still a need to clarify disease-elicited mechanisms and how aSyn has the ability to modulate mitochondrial and cellular dysfunction, recent studies provide insightful views on mitochondria-inflammation axis in PD etiology.

Cited by (0)