Rescuing early Parkinson-induced hyposmia prevents dopaminergic system failure [human]
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PROVIDER: PRJNA985706 | ENA |
REPOSITORIES: ENA
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Project description:Rescuing early Parkinson-induced hyposmia prevents dopaminergic system failure
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Project description:The diagnosis of Parkinsonism is based on motor symptoms that are caused by reduced dopaminergic output However, decades earlier, patients report non-motoric problems, including hyposmia It is not known if non-motor and motor defects are causally connected Here we used single-cell transcriptome sequencing (10x) of young and olf fly mutants (whole brain) and human patients (three regions: nucleus basalis of Meynert, nucleus accumbens and putamen). This atlas reveals early defects in cholinergic neurons that are recapitulaed across species
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Project description:The diagnosis of Parkinsonism is based on motor symptoms that are caused by reduced dopaminergic output However, decades earlier, patients report non-motoric problems, including hyposmia It is not known if non-motor and motor defects are causally connected Here we used single-cell transcriptome sequencing (10x) of young and olf fly mutants (whole brain) and human patients (three regions: nucleus basalis of Meynert, nucleus accumbens and putamen). This atlas reveals early defects in cholinergic neurons that are recapitulaed across species
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Project description:This SuperSeries is composed of the SubSeries listed below.
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Project description:Parkinson disease (PD) is the second most common age-related neurodegenerative disorder, which is related to neurotransmitter secretion impartment and the dysfunction of vesicle transport. Secretory granules (SGs) are a class of intracellular vesicles different from synaptic vesicles (SVs) in neurons and the neuroendocrine cells. They represent the primary subcellular site for the biosynthesis, storage and releasing of the neuropeptides, neurotransmitters and hormones. In the current study, we characterized the proteome of secretory granules in dopaminergic neurons in PD. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was used to identify proteins in SGs. A total of 4249 proteins were identified in the SGs in normal and MPP+-treated SH-Sy5Y dopaminergic neurons in total. This study regarded the biological alternations of SGs in PD as an entry point. By studying the significantly differentially expressed proteins, it is helpful to better understand the molecular mechanisms of SGs disorders in the pathology of PD, and provide a basis for vesicle transport theory in pathogenesis of PD.
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Project description:Identification of Drug Candidates Rescuing SARS-CoV-2 Infection Induced Dopaminergic Neuron Senescence
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Project description:Engrailed homeoproteins are expressed in adult dopaminergic neurons of the substantia nigra. In Engrailed1 heterozygous mice, these neurons start dying at 6 weeks, are more sensitive to oxidative stress and progressively develop traits similar to those observed following an acute and strong oxidative stress inflected to wild-type neurons. These changes include DNA strand breaks and the modification (intensity and distribution) of several nuclear and nucleolar heterochromatin marks. Engrailed1 and Engrailed2 are biochemically equivalent transducing proteins previously used to antagonize dopaminergic neuron death in Engrailed heterozygous mice and in mouse models of Parkinson disease. Accordingly, we show that, following an acute oxidative stress, a single Engrailed2 injection restores all nuclear and nucleolar heterochromatin marks, decreases the number of DNA strand breaks and protects dopaminergic neurons against apoptosis. RNA-seq data for differentially expressed genes in the SNpc of En1+/- mice, En2 infused mice and 6-OHDA/En2 injection experiments.
2015-09-24 | E-GEOD-72321 | biostudies-arrayexpress
Project description:Circadian rhythm dysfunction is a hallmark of Parkinson Disease (PD), and diminished expression of the core clock gene Bmal1 has been described in PD patients. BMAL1 is required for core circadian clock function, but also serves non-rhythmic functions. Germline Bmal1 deletion can cause brain oxidative stress and synapse loss in mice, and can exacerbate dopaminergic neurodegeneration in response to MPTP. Here we examined the impact of cell type-specific Bmal1 deletion on dopaminergic neuron viability in vivo. We observed that global, post-natal deletion of Bmal1 caused spontaneous loss of tyrosine hydroxylase-positive (TH+) dopaminergic neurons in the substantia nigra pars compacta (SNpc). This was not due to disruption of behavioral circadian rhythms, and was not induced by astrocyte- or microglia-specific Bmal1 deletion. However, either pan-neuronal or TH neuron-specific Bmal1 deletion caused cell-autonomous loss of TH+ neurons in the SNpc. Finally, global Bmal1 deletion exacerbated TH+ neuron loss following injection of alpha-synclein fibrils. Transcriptomic analysis of neuron-specific Bmal1 KO brain revealed dysregulation of pathways involved in oxidative phosphorylation and Parkinson Disease.
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Project description:Engrailed homeoproteins are expressed in adult dopaminergic neurons of the substantia nigra. In Engrailed1 heterozygous mice, these neurons start dying at 6 weeks, are more sensitive to oxidative stress and progressively develop traits similar to those observed following an acute and strong oxidative stress inflected to wild-type neurons. These changes include DNA strand breaks and the modification (intensity and distribution) of several nuclear and nucleolar heterochromatin marks. Engrailed1 and Engrailed2 are biochemically equivalent transducing proteins previously used to antagonize dopaminergic neuron death in Engrailed heterozygous mice and in mouse models of Parkinson disease. Accordingly, we show that, following an acute oxidative stress, a single Engrailed2 injection restores all nuclear and nucleolar heterochromatin marks, decreases the number of DNA strand breaks and protects dopaminergic neurons against apoptosis.
2015-09-24 | GSE72321 | GEO