Research Paper Volume 13, Issue 16 pp 20335—20358
Proteomic characterization of secretory granules in dopaminergic neurons indicates chromogranin/secretogranin-mediated protein processing impairment in Parkinson’s disease
- 1 School of Forensic Medicine, China Medical University, Shenyang, PR China
- 2 Department of Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang, PR China
Received: May 12, 2021 Accepted: August 3, 2021 Published: August 21, 2021
https://doi.org/10.18632/aging.203415How to Cite
Copyright: © 2021 Wen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Parkinson’s disease (PD) is an aging disorder related to vesicle transport dysfunctions and neurotransmitter secretion. Secretory granules (SGs) are large dense-core vesicles for the biosynthesis of neuropeptides and hormones. At present, the involvement of SGs impairment in PD remains unclear. In the current study, we found that the number of SGs in tyrosine hydroxylase-positive neurons and the marker proteins secretogranin III (Scg3) significantly decreased in the substantia nigra and striatum regions of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) exposed mice. Proteomic study of SGs purified from the dopaminergic SH-sy5Y cells under 1-methyl-4-phenylpyridinium (MPP+) treatments (ProteomeXchange PXD023937) identified 536 significantly differentially expressed proteins. The result indicated that disabled lysosome and peroxisome, lipid and energy metabolism disorders are three characteristic features. Protein-protein interaction analysis of 56 secretory proteins and 140 secreted proteins suggested that the peptide processing mediated by chromogranin/secretogranin in SGs was remarkably compromised, accompanied by decreased candidate proteins and peptides neurosecretory protein (VGF), neuropeptide Y, apolipoprotein E, and an increased level of proenkephalin. The current study provided an extensive proteinogram of SGs in PD. It is helpful to understand the molecular mechanisms in the disease.
Abbreviations
PD: Parkinson’s disease; SGs: secretory granules; Scg2: Secretogranin II; Scg3: Secretogranin III; CgA: chromogranin A; CgB: chromogranin B; PQ: paraquat; LC-MS/MS: liquid chromatography-tandem mass spectrometry; CPE: carboxypeptidase E; SNpc: nigra pars compacta; DCVs: dense-core vesicles; SVs: synaptic vesicles; NPY: neuropeptide Y; BDNF: neurotrophic factor; VGF: neurosecretory protein; NPY: neuropeptide Y; APOE: Apolipoprotein E; PDYN: prodynorphin; AD: Alzheimer's disease; HD: Huntington's disease.