Mitochondrial-Dysfunction

Cross-tall between mitochondrial dysfunction and neuroinflammation (in PD, ICM)
=> HSD17b10 and TFAM in CSF

NeuroMMSig mitochondrial subgraph:

Mitochondrial dysfunction in PD is strongly suported by the association of parkinsonism due to or associated with mitocondrial toxines (MPTP, rotenone, paraquat), the involvement of causal genes of PD in mitocondria processes (Parkin, Pink), and the complex I deficiency observed in PD brains and animal models.

Recent studies have suggested a role of Parkin in innate immunity and our unpublished data support a cross-talk between Parkin-dependent mitophagy impairment and over-activation of microglia in PD models. Because PD associated with Parkin and Pink1 mutations is associated with a specific young onset, pure motor phenotype of the disease, we hypothezise that we will be able to identify a cluster of patients sharing a similar and common bioligical mechanisms and potentially common phenotype in the common sporadic form of PD.

Many SNPs are associated with TOMM40 in the context of AD. TOMM40 together with TIMM23 binds with amyloid beta peptides when there is mitochondrial dysfunction. This leads to accumulation of amyloid beta peptides.
NeuroMMSig mitochondrial translocation subgraph:

Cartoon of the candidate mechanisms: