Table 1 PD risk genes that affect bone metabolism
From: Parkinson's in the bone
Gene (symbol) | Chromosomal location | Inheritance | Biological function | Phenotype |
|---|---|---|---|---|
FBXO7 (PARK15) | 4q22.1 | AD | Regulate proteasome-independent ubiquitination of NRAGE | Increase BMP4-mediated signaling in HEK293 cells [40] |
HTRA2 (PARK13) | 2p13.1 | AD | Enhanced the stability of TNF receptor-associated factor 2; | Activation of the inflammatory response in mouse arthritis model [79] |
LRRK2 (PARK8) | 12q12 | AD | Inhibit canonical Wnt signaling, decrease the levels of transcriptionally active β-catenin | Lrrk2-KO mice shown increased tibial cortical bone strength [47] |
NR4A2 (NURR1) | 2q22-q23 | Risk factor | NR4A2 expression was induced by PTH-cAMP/PKA pathway; Enhanced the transcription of FGF23; Activate the OPN promoter | |
DJ-1 (PARK7) | 1p36.23 | AR | Decrease intracellular ROS concentration and increase the activity of SHP-1 during osteoclastogenesis; Activate FGF receptor-1 signaling | Increase bone mass via negatively regulation of osteoclastogenesis and promotes osteoblasts differentiation [31, 32] |
PINK1 (PARK6) | 1q36.12 | AR | Regulate mitophagy | Play a protective role in bone impairment [24] |
PRKN (PARK2) | 6q26 | AR | Regulate mitophagy; promoteβ-catenin expression and autophagy | Play a protective role in bone impairment; Promote osteoblastic differentiation and accelerate bone healing in mouse model [24,25,26] |
SNCA (PARK1; PARK4) | 4q22.1 | AD | a key mediator of the expression of specific network modules and the skeletal response to estrogen deficiency | |
UCHL1 (PARK5) | 4p13 | AD | A component of the ubiquitin proteasome system | Regulates bone mineralization during osteogenesis in mouse model [37] |
VPS35 (PARK17) | 16q11.2 | AD | Terminate PTH signaling in OBs; Inhibit RANKL signaling in OCs | Promote bone formation and inhibit bone resorption in mouse model [57, 58] |