Dataset Information

Multi-omics approach identifies a network of lipids and proteins associated to lysosomal and mitochondrial metabolism in Parkinson’s disease patients carrying mutations in TMEM175 gene.

ABSTRACT: Parkinson’s disease (PD) represents one of the most frequent neurodegenerative disorders for which clinically useful biomarkers remain to be identified and validated for early and more precise diagnosis or for differentiation of disease subtypes, which may require different treatments. In this study we adopted an untargeted omics approach to disclose lipidomic, metabolomic and proteomic alterations in PD patients carrying TMEM175 mutations both in plasma and dermal fibroblasts. Integrated analysis of omics data revealed a wide dysregulation of lysosome, autophagy, and mitochondrial pathways in these PD patients, supporting a relevant role of this channel in regulating these cellular processes. The most significant altered lipid classes (CAR, Cer, FA, HexCer, PC, PC O-, SM, PI), and enzymes (PAG15, PP4P1, GALC, FYV1, PIGO, PGPS1, PLPP1) were involved in phosphosphingolipids and glycerophospholipids biosynthetic pathways. We also disclosed alterations of proteins involved in the insulin pathway (IGF2R), mitochondrial metabolism (ACD10, ACD11, ACADS) and autophagy (RAB7L). Interestingly, we also highlighted that the levels of CAR 18:2, HexCer 42:1;3O, and HexCer 42:2;3O, negatively correlated with age and age at onset (AAO) in PD patients. Strikingly, PI 34:1 was the only lipid showing a significant association with disease and a significant correlation (r=−0.5509; p=0.006) with age and earlier AAO of disease only in TMEM175 PD patients. All together these data provide novel insights into the molecular and metabolic alterations underlying TMEM175 mutations and may be relevant for PD prediction, diagnosis and treatment.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Fibroblast, Extracellular Exosome

DISEASE(S): Peripheral Primitive Neuroectodermal Tumor,Parkinson's Disease

SUBMITTER: Marcello Manfredi

LAB HEAD: Marcello Manfredi

PROVIDER: PXD049990 | Pride | 2025-05-06

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	CNR_10_200ngul_DMSO_06092023_Lib1.mgf	Mgf
	CNR_11_200ngul_DMSO_06092023_Lib1.mgf	Mgf
	CNR_12_200ngul_DMSO_06092023_Lib1.mgf	Mgf
	CNR_17_200ngul_DMSO_06092023_Lib1.mgf	Mgf
	CNR_18_200ngul_DMSO_06092023_Lib1.mgf	Mgf

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Multiomics approach identifies dysregulated lipidomic and proteomic networks in Parkinson's disease patients mutated in TMEM175.

Carrillo Federica F Ghirimoldi Marco M Fortunato Giorgio G Palomba Nicole Piera NP Ianiro Laura L De Giorgis Veronica V Khoso Shahzaib S Giloni Tiziana T Pietracupa Sara S Modugno Nicola N Barberis Elettra E Manfredi Marcello M Esposito Teresa T

NPJ Parkinson's disease 20250124 1

Parkinson's disease (PD) represents one of the most frequent neurodegenerative disorders for which clinically useful biomarkers remain to be identified and validated. Here, we adopted an untargeted omics approach to disclose lipidomic, metabolomic and proteomic alterations in plasma and in dermal fibroblasts of PD patients carrying mutations in TMEM175 gene. We revealed a wide dysregulation of lysosome, autophagy, and mitochondrial pathways in these patients, supporting a role of this channel in ...[more]

PMID: 39856101

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