Matrisome changes in Parkinson’s disease

Extracellular matrix (ECM) proteins, including collagens, glycoproteins, and proteoglycans, are known as the matrisome. Alterations in the matrisome have been associated with neurodegenerative disorders such as Parkinson’s disease (PD). The PD brain can be characterised by the development of Lewy bodies in brain regions such as prefrontal cortex (PFC). In this recent study, the researchers investigated the alterations in the expression and modification of the matrisome in the PFC of PD and control individuals by label free quantification analysis via liquid chromatography-tandem mass spectrometry (LC–MS/MS). Unique proteomic and glycomic changes were found in the PFC of the individuals affected with PD. Specifically, significantly higher type I collagen was found in the PFC of the PD brain compared with age-matched controls and young controls, and more pronounced changes were observed in the PD brains relative to normal ageing brains. Approximately 50% of hydroxylation on proline residues in type I collagen was observed in the PD brain, while more variability was observed in young and aged brains. In addition, the abundance of the glycopeptide from collagen alpha-3(VI) chain (COL6A3) was elevated in PD individuals when compared to controls. Moreover, an increased level of versican, a core ECM proteoglycan, and a decreased glycosylation fraction of versican were observed in PD relative to aged controls. These findings collectively revealed unique PFC matrisome changes associated with PD.

How was PEAKS used?

LC–MS/MS data were collected from the PFC of fresh-frozen human brain tissues. The data were analysed using PEAKS X+ for label free quantitation. The variable modifications including hydroxylation P, deamidation N, oxidation M, phosphorylation STY, HexNAc ST, HexHexNAc ST, hydroxylation K, hydroxylation-Hex K, hydroxylation Hex-Hex K, ubiquitination K, and nitrotyrosine Y were added. The parameters were set with a de novo score greater than 15%, a precursor mass tolerance of 10 ppm, a fragment mass tolerance of 0.02 Da, and a maximum of 3 missed cleavages.

Downs, M., Sethi, M.K., Raghunathan, R. et al. Matrisome changes in Parkinson’s disease. Anal Bioanal Chem 414, 3005–3015 (2022). doi:10.1007/s00216-022-03929-4


Extracellular matrix (ECM) proteins, collectively known as the matrisome, include collagens, glycoproteins, and proteoglycans. Alterations in the matrisome have been implicated in the neurodegenerative pathologies including Parkinson’s disease (PD). In this work, we utilized our previously published PD and control proteomics data from human prefrontal cortex and focused our analysis on the matrisome. Among matrisome proteins, we observed a significant enrichment in the expression of type I collagen in PD vs. control samples. We then performed histological analysis on the same samples used for proteomics study, and examined collagen expression using picrosirius red staining. Interestingly, we observed similar trends in collagen abundance in PD vs. control as in our matrisome analysis; thus, this and other histological analyses will be useful as a complementary technique in the future to study the matrisome in PD with a larger cohort, and it may aid in choosing regions of interest for proteomic analysis. Additionally, collagen hydroxyprolination was less variable in PD compared to controls. Glycoproteomic changes in matrisome molecules were also observed in PD relative to aged individuals, especially related to type VI collagen and versican. We further examined the list of differentially expressed matrisome molecules using network topology-based analysis and found that angiogenesis indicated by alterations in decorin and several members of the collagen family was affected in PD. These findings collectively identified matrisome changes associated with PD; further studies with a larger cohort are required to validate the current results.