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Parkinson's disease (PD) is the second most common neurodegenerative disorder, with a lifetime risk of 2% for men and 1.
Parkinson's disease (PD) is the second most common neurodegenerative disorder, with a lifetime risk of 2% for men and 1.
Figure 1 Title map of the paper
Figure 1 Title map of the paperThe etiology and pathophysiology of sporadic Parkinson's disease have not been elucidated, hindering the development of effective disease-modifying treatments
The etiology and pathophysiology of sporadic Parkinson's disease have not been elucidated, hindering the development of effective disease-modifying treatments
This unbiased, hypothesis-generating approach not only confirmed processes and pathways previously implicated in PD pathology (i.
Lipids are primarily known for their role in energy storage, but they are also major components of cell membranes, part of membrane rafts and anchors, as well as signaling and transport molecules
The classification of such lipids is based on their chemical and biochemical properties
Briefly, fatty acyl groups are lipids synthesized from chain elongation of acetyl-CoA, the building blocks of complex lipids
Glycerophospholipids (or phospholipids) have a glycerol backbone and a polar head group and can distinguish several subclasses, including phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and lysophosphatidylethanolamine (LPE)
Blood and cellular composition and levels are regulated by multiple factors, such as lipid intake, gut microbiota, microRNAs (eg, miR-33 and miR-122), and regulatory proteins, such as sterol regulatory element-binding protein, liver X receptors, p53 and AMPK
In addition, fatty acid transport occurs in conjunction with other proteins such as albumin
To investigate the genetic overlap between PD and lipid levels, Helena Xicoy et al.
They found a common genetic etiology between PD and the levels of 25 lipids in the blood
They then used data from a broader PD GWAS to try to confirm the findings
Figure 2 Schematic diagram of Parkinson's lipid metabolites
Figure 2 Schematic diagram of Parkinson's lipid metabolitesIn both analyses, we found genetic overlap between PD and blood levels of eight lipids, namely two polyunsaturated fatty acids (PUFA 20:3n3-n6 and 20:4n6), four triacylglycerols ( TAG 44:1, 46:1, 46:2 and 48:0), phosphatidylcholine aa 32:3 (PC aa 32:3) and sphingosine 26:0 (SM 26:0)
In both analyses, we found genetic overlap between PD and blood levels of eight lipids, namely two polyunsaturated fatty acids (PUFA 20:3n3-n6 and 20:4n6), four triacylglycerols ( TAG 44:1, 46:1, 46:2 and 48:0), phosphatidylcholine aa 32:3 (PC aa 32:3) and sphingosine 26:0 (SM 26:0)
Analysis of concordance (consistency in direction of effect of genetic variation across two traits) showed significant negative concordance between PD and blood levels of the four triacylglycerols and PC aa 32:3, as well as between PD and PUFA Positive concordance with blood levels of SM 26:0
.
Taken together, these analyses suggest that genetic variants associated with PD modulate blood levels of specific lipid species , supporting a critical role for these lipids in the etiology of PD
.
.
Genetic variants associated with PD that regulate blood levels of specific lipid species
Original source:
Xicoy H, Klemann CJ, De Witte W, Martens MB, Martens GJ, Poelmans G.
Shared genetic etiology between Parkinson's disease and blood levels of specific lipids.
npj Parkinsons Dis.
2021;7(1):23.
doi: 10.
1038/s41531-021-00168-9
Original source:
Xicoy H, Klemann CJ, De Witte W, Martens MB, Martens GJ, Poelmans G.
Shared genetic etiology between Parkinson's disease and blood levels of specific lipids.
npj Parkinsons Dis.
2021;7(1):23.
doi: 10.
1038/s41531-021-00168-9 Shared genetic etiology between Parkinson's disease and blood levels of specific lipids.
npj Parkinsons Dis.
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