Dataset Information

Cell-Cell Communication Alterations via Intercellular Signaling Pathways in Substantia Nigra of Parkinson's Disease.

ABSTRACT: Parkinson's disease (PD) is a neurodegenerative movement disorder characterized with dopaminergic neuron (DaN) loss within the substantia nigra (SN). Despite bulk studies focusing on intracellular mechanisms of PD inside DaNs, few studies have explored the pathogeneses outside DaNs, or between DaNs and other cells. Here, we set out to probe the implication of intercellular communication involving DaNs in the pathogeneses of PD at a systemic level with bioinformatics methods. We harvested three online published single-cell/single-nucleus transcriptomic sequencing (sc/snRNA-seq) datasets of human SN (GSE126838, GSE140231, and GSE157783) from the Gene Expression Omnibus (GEO) database, and integrated them with one of the latest integration algorithms called Harmony. We then applied CellChat, the latest cell-cell communication analytic algorithm, to our integrated dataset. We first found that the overall communication quantity was decreased while the overall communication strength was enhanced in PD sample compared with control sample. We then focused on the intercellular communication where DaNs are involved, and found that the communications between DaNs and other cell types via certain signaling pathways were selectively altered in PD, including some growth factors, neurotrophic factors, chemokines, etc. pathways. Our bioinformatics analysis showed that the alteration in intercellular communications involving DaNs might be a previously underestimated aspect of PD pathogeneses with novel translational potential.

SUBMITTER: Huang M

PROVIDER: S-EPMC8914319 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Cell-Cell Communication Alterations <i>via</i> Intercellular Signaling Pathways in Substantia Nigra of Parkinson's Disease.

Huang Maoxin M Xu Liang L Liu Jin J Huang Pei P Tan Yuyan Y Chen Shengdi S

Frontiers in aging neuroscience 20220225

Parkinson's disease (PD) is a neurodegenerative movement disorder characterized with dopaminergic neuron (DaN) loss within the substantia nigra (SN). Despite bulk studies focusing on intracellular mechanisms of PD inside DaNs, few studies have explored the pathogeneses outside DaNs, or between DaNs and other cells. Here, we set out to probe the implication of intercellular communication involving DaNs in the pathogeneses of PD at a systemic level with bioinformatics methods. We harvested three o ...[more]

PMID: 35283752

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Project description:BackgroundParkinson's disease (PD) is the most common neurodegenerative disorder involving the motor system. Although not being the only region involved in PD, affection of the substantia nigra and its projections is responsible for some of the most debilitating features of the disease. To further advance a comprehensive understanding of nigral pathology, we conducted a tissue based comparative proteome study of healthy and diseased human substantia nigra.ResultsThe gross number of differentially regulated proteins in PD was 221. In total, we identified 37 proteins, of which 16 were differentially expressed. Identified differential proteins comprised elements of iron metabolism (H-ferritin) and glutathione-related redox metabolism (GST M3, GST P1, GST O1), including novel redox proteins (SH3BGRL). Additionally, many glial or related proteins were found to be differentially regulated in PD (GFAP, GMFB, galectin-1, sorcin), as well as proteins belonging to metabolic pathways sparsely described in PD, such as adenosyl homocysteinase (methylation), aldehyde dehydrogenase 1 and cellular retinol-binding protein 1 (aldehyde metabolism). Further differentially regulated proteins included annexin V, beta-tubulin cofactor A, coactosin-like protein and V-type ATPase subunit 1. Proteins that were similarly expressed in healthy or diseased substantia nigra comprised housekeeping proteins such as COX5A, Rho GDI alpha, actin gamma 1, creatin-kinase B, lactate dehydrogenase B, disulfide isomerase ER-60, Rab GDI beta, methyl glyoxalase 1 (AGE metabolism) and glutamine synthetase. Interestingly, also DJ-1 and UCH-L1 were expressed similarly. Furthermore, proteins believed to serve as internal standards were found to be expressed in a constant manner, such as 14-3-3 epsilon and hCRMP-2, thus lending further validity to our results.ConclusionUsing an approach encompassing high sensitivity and high resolution, we show that alterations of SN in PD include many more proteins than previously thought. The results point towards a heterogeneous aetiopathogenesis of the disease, including alterations of GSH-related proteins as well as alterations of proteins involved in retinoid metabolism, and they indicate that proteins involved in familial PD may not be differentially regulated in idiopathic Parkinson's disease.

Dataset Information

Cell-Cell Communication Alterations via Intercellular Signaling Pathways in Substantia Nigra of Parkinson's Disease.

Publications

Cell-Cell Communication Alterations <i>via</i> Intercellular Signaling Pathways in Substantia Nigra of Parkinson's Disease.

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