| PXD000547 | Corpus Callosum | Proteome of the Human Corpus Callosum | Characterization of the human Anterior Temporal Lobe and Corpus Callosum: C-HPP |
| PXD000548 | Anterior Temporal Lobe | Proteome analyses of the human anterior temporal lobe | Characterization of the human Anterior Temporal Lobe and Corpus Callosum: C-HPP |
| PXD000742 | Caudate Nucleus | Caudate nucleus proteome | In order to analyse thecaudate nucleus proteome in a large-scale format, we used a multi-dimensional fractionation approach which combines isolation of anatomically-defined nuclei, and protein/peptide chromatographic fractionation strategies coupled to mass spectrometry. |
| PXD000749 | Putamen | Putamen proteme | In order to analyse the putamen proteome in a large-scale format, we used a multi-dimensional fractionation approach which combines isolation of anatomically-defined nuclei, and protein/peptide chromatographic fractionation strategies coupled to mass spectrometry. |
| PXD001255 | Dendritic Spine | Sequential elution interactome analysis of Mind bomb 1 and a novel role in dendritic spine outgrowth | Mind bomb 1 (Mib1) is an E3 ubiquitin-ligase that is essential for overall metazoan development, including multiple stages of neuronal development. It is located in puncta throughout neurons, including near post synaptic densities (PSD), and has been shown to participate in several signaling pathways via its E3 ligase catalytic activity. The most well-characterized of these is the Notch signaling pathway, in which Mib1 facilitates Delta/Serrate/LAG-2 (DSL) ligand endocytosis and activation, allowing cell-cell communication to determine neuronal versus glial cell fate. This, however, is not the limit of Mib1 activity in the developing nervous system, as it also contributes to cell polarity, neurite outgrowth, and long-term potentiation (LTP), but it has not been demonstrated to affect dendritic spine development. We therefore sought to comprehensively characterize the Mib1 interactome and study its potential function in dendritic spine morphogenesis. We utilized a novel sequential elution method from Mib1 affinity purification to recover Mib1 binding proteins with both deep coverage and the ability to distinguish between high affinity binding partners from low affinity binding partners. This procedure revealed 837 potential binding partners, distinguished 72 from these as very-high confidence, and a further 387 as high confidence of interaction. Included in these were many proteins previously demonstrated to interact with Mib1, as well as 5 proteins of particular interest to us: Usp9x, a deubiquitinase; alpha-, beta-, and delta-catenins; regulators of Wnt signaling; and CDKL5, which is mutated in EIEE2, a severe form of mental retardation. We demonstrated that Mib1 downregulates CDKL5, limits its effects on dendritic spine outgrowth, and inhibits spine outgrowth itself. These data further elaborate upon the signaling networks and biological functions influenced by this critical protein and expand our understanding of the signaling networks involved in neuronal development. |
| PXD001987 | Hippocampus | TMT-labeled quantitative protein profiling of hippocampus during human aging | Human hippocampus is one of the critical brain regions affected by aging. However, a fully understanding of aging-related changes in protein profiles in human hippocampus has not been well described, especially for the Chinese population. With the newly founded human brain bank in Chinese Academy of Medical Sciences & Peking Union Medical College, we performed a 4-plex TMT labeled proteomic study in the hippocampus of postmortem human brains. The ages of death ranged from 22-98, and were grouped into 4 aging groups: 20-50, 50-70, 70-90, and over 90 (n=4 each). None of the donors was diagnosed with neurodegenerative diseases according to their medical history. Our data identified 4582 proteins, among which 99 proteins were upregulated and 42 proteins were downregulated during the aging process. |
| PXD004076 | Cerebrum | Spatiotemporal proteomic profiling of human cerebral development | We utilize a rapid shotgun LFQ MS method to profile four regions of developing human cerebrum. Regions encompass neural precursor rich ventricular zone, intermediate, subplate and cortex regions across human development from gestational week 16-36 and postnatal week 41 and adult brain tissue. |
| PXD004987 | Substantia Nigra | Proteomic characterization of neuromelanin granules isolated from human substantia nigra by laser-microdissection | Neuromelanin is a complex polymer pigment found primarily in the dopaminergic neurons of human substantia nigra. Neuromelanin pigment is stored in granules including a protein matrix and lipid droplets. Neuromelanin granules are yet only partially characterised regarding their structure and function. To clarify the exact function of neuromelanin granules in humans, their enrichment and in-depth characterization from human substantia nigra is necessary. Previously published global proteome studies of neuromelanin granules in human substantia nigra required high tissue amounts. Due to the limited availability of human brain tissue we established a new method based on laser microdissection combined with mass spectrometry for the isolation and analysis of neuromelanin granules. With this method it is possible for the first time to isolate a sufficient amount of neuromelanin granules for global proteomics analysis from ten 10 µm tissue sections. In total 1,000 proteins were identified associated with neuromelanin granules. More than 68% of those proteins were also identified in previously performed studies. Our results confirm and further extend previously described findings, supporting the connection of neuromelanin granules to iron homeostasis and lysosomes, respectively endosomes. Hence, this method is suitable for the donor specific enrichment and proteomic analysis of neuromelanin granules. |
| PXD005629 | Olfactory Bulb | A proteomic analysis of human olfactory bulb | Olfactory sensory neurons distinguish a large variety of odor molecules and direct the information through their axons to the olfactory bulb, the first site for the processing of olfactory information in the brain. Olfaction is very important for most mammals for the maintenance of a good quality of life. Accumulating evidences endorse that olfactory sensory decline is connected with neurodegenerative disorders including schizophrenia, depression, multiple sclerosis, Huntington's, Alzheimer's and Parkinson's diseases. For several decades, neuroanatomical, volumetric, and histological approaches have been the gold standard techniques employed to characterize the olfactory bulb functionality. Diagnosis and treatment of olfactory dysfunction remain significant health care challenges to society. Novel strategies and clues that assist in the identification of biomarker and drug development for aid in the prevention and cure of neurological diseases are necessary. However, little attention has been focused specifically on the molecular composition of the olfactory bulb from the perspective of proteomics. To this end, an in-depth mapping of the olfactory bulb proteome was carried out using high resolution tandem mass spectrometry, revealing a repertoire of 7,754 proteins. A large proportion of the identified proteins were predicted to be involved in diverse biological processes including signal transduction, metabolism, transport, olfaction and protein synthesis. Pathway analysis of the identified proteins shows that, these proteins are predominantly involved in metabolic and neural processes, chromatin modeling, and synaptic vesicle transport associated with neuronal transmission. In total, our study offers valuable understandings into the molecular composition of the human olfactory bulb proteome that could possibly help neuroscience community to understand the olfactory bulb better and open avenues for intervention strategies for olfactory dysfunction in the future. |
| PXD006471 | Pituitary Gland | A Comprehensive map and functional annotation of human pituitary and thyroid proteome | A Comprehensive map and functional annotation of human pituitary and thyroid proteome |
| PXD008625 | Brain | Cracking the code of an elusive key protein modification at structural and genome scales | Characterization of Myristoylated proteins in human brain and liver samples. |
