Table 1.
Neuroinflammation relevant genes in PD
| Gene | Locus | Location | Inheritance | Phenotype | Gene function | Neuropathology | Reference |
|---|---|---|---|---|---|---|---|
| SNCA | PARK1/4 | 4q22.1 |
AD Sporadic |
Early-onset PD |
1. Presynaptic vesicular neurotransmission 2. Neuroinflammation modulation |
1. Facilitating pro-inflammatory milieu formation 2. Neurodegeneration in SN 3. Widespread LBs formation |
[33–35, 40, 50–52] |
| LRRK2 | PARK8 | 12q12 |
AD Sporadic |
Classical PD |
1. Neuroinflammation modulation 2. Dynamic cytoskeletal regulation 3. Autophagy accommodation |
1. Microglial phenotype switch (M2–M1) 2. Inflammation exacerbation 3. LBs formation and nigral neurons loss |
[54–57] |
| Parkin | PARK2 | 6q25.2-7 |
AR Sporadic |
Juvenile and early onset PD |
1. Encoding protein containing E3 ligase activity 2. Involved in UPS 3. Preventing protein aggregation and promoting mitophagy 4. Adaptive immunity regulation |
1. Increase susceptibility to inflammation-induced neurodegeneration 2. Absence of LBs 3. Dopaminergic neuronal loss in SN |
[58–61] |
| PINK1 | PARK6 | 1p36.12 | AR | Early-onset PD |
1. Encoding PTEN-induced putative kinase 1 (mitochondrial kinase) 2. Stabilize mitochondrial function during episodes of cellular stress 3. Adaptive immunity regulation |
1. Increase vulnerability to neuroinflammation 2. Dopaminergic neuron loss in SN 3. Far-ranging LBs formation |
[61, 62] |
| DJ-1 | PARK7 | 1p36.23 | AR | Early-onset PD |
1. Encoding the redox sensor DJ-1 2. Protecting cell from oxidative stress response 3. Associate with HSP70 to mediate PTM or repair misfolded protein 4. Involved in PD-related cellular pathway as a RNA binding protein |
1. Increase susceptibility to PD-related environmental toxins 2. Enable dopaminergic neurons sensitive to oxidative stress and proteasomal inhibition |
[65–72] |
| ATP13A2 | PARK9 | 1p36 | AR | Early-onset levodopa responsive parkinsonism (KRS) |
1. Encoding transmembrane lysosomal P5 type ATPase 2. Involved in ALP 3. Facilitating lysosome function and preventing protein aggregation 4. Mediating neuroinflammation via NLRP3 inflammasome |
1. Dopaminergic neurons loss in SN 2. Enable lysosome dysfunction and protein aggregates accumulation 3. Inducing NLRP3 inflammasome-mediated dopaminergic neurodegeneration |
[73, 74, 78] |
AD autosomal dominant, AR autosomal recessive, PTM post-transcriptional modification, UPS ubiquitin–proteasome system, ALP autophagy lysosome pathway, KRS Kulfor–Rakeb syndrome