Figure legends
Figure 1: Vitamin D absorption, metabolism, and transport in blood. The various sources of vitamin D precursors and their two-step activation to form calcitriol (α-1,25 (OH)2D3) which further binds with VDR and DBP to explicit its functions. DBP, Vitamin D binding protein; RXR, retinoid X receptor; VDR, vitamin D receptor; CYP27B1, 1-OHase; CYP2R1, 25-hydroxyvitamin D-1α- hydroxylase; CYP24A1, 24-OHase.
Figure 2 : Network analysis of the genes linked with Parkinson’s disease . 2A. Gene-disease association (GDA) analysis in Parkinson’s disease and protein-protein interaction (PPI) network. 2B. The top 5 genes (as obtained from Fig 2A) (hub/core). IL-6, TNF, STAT3. ILIB and CXCL8 within the network were found using the cytoHubba plugin of the Cytoscape application. 2C. Linkage between VDR and TNF along with other inflammatory genes in PD.
Figure 3: The possible inflammatory pathway linkages between Vitamin D deficiency and Parkinson’s disease . Polymorphisms of Vitamin D-associated genes, low sunlight exposure, and/or inadequate dietary intake results in VDD leading to increased pro-inflammatory cytokine production and decreased anti-inflammatory cytokine production and downregulated calbindin-D28k causing α-synuclein aggregation. Incompetent VDR results in increased extra-renal 1,25-dihydroxy vitamin D, which enhances inflammation and decreases 25-hydroxy vitamin D. Microbial infection also increases pro-inflammatory cytokine production and upregulates α-synuclein production, which later forms α-synuclein aggregates leading to neuronal degeneration and then PD.