Involvement of Endocytosis and Alternative Splicing in the Formation of the Pathological Process in the Early Stages of Parkinson’s Disease

Alieva, Anelya Kh.; Шадрина, М. И.; Filatova, Elena V.; Karabanov, Alexander; Иллариошкин, С. Н.; Limborska, Svetlana A.; Slominsky, Petr

doi:10.1155/2014/718732

Cited by 30 publications

(26 citation statements)

References 45 publications

(46 reference statements)

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“…Microarray studies have been valuable in identifying differential gene expression patterns and perturbed biological processes in blood of PD patients (Mutez et al, 2011; Potashkin et al, 2012; Alieva et al, 2014; Calligaris et al, 2015; Santiago and Potashkin, 2015; Santiago et al, 2016; Simchovitz et al, 2016). For example, high-throughput screening of blood RNA have provided molecular clues for some of the dysregulated pathways in PD, including the impairment of insulin signaling and glucose metabolism (Santiago and Potashkin, 2013a,b, 2015), aberrant RNA splicing (Potashkin et al, 2012; Soreq et al, 2012; Alieva et al, 2014), and inflammation (Simchovitz et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…For example, high-throughput screening of blood RNA have provided molecular clues for some of the dysregulated pathways in PD, including the impairment of insulin signaling and glucose metabolism (Santiago and Potashkin, 2013a,b, 2015), aberrant RNA splicing (Potashkin et al, 2012; Soreq et al, 2012; Alieva et al, 2014), and inflammation (Simchovitz et al, 2016). Besides these pathways, disrupted iron metabolism has been implicated in the pathogenesis of PD, but the mechanisms underlying this association remain uncertain.…”

Section: Discussionmentioning

confidence: 99%

“…Since high-throughput screening of RNA from blood has been instrumental in elucidating important molecular pathways underlying neurodegeneration in PD patients (Scherzer et al, 2007; Mutez et al, 2011; Potashkin et al, 2012; Alieva et al, 2014; Calligaris et al, 2015; Santiago et al, 2016; Simchovitz et al, 2016), we hypothesized that analysis of the blood transcriptome could provide clues for the disrupted iron metabolism observed in PD patients. To this end, we performed a meta-analysis of four independent blood microarrays from PD patients and HCs.…”

Section: Introductionmentioning

confidence: 99%

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Blood Transcriptomic Meta-analysis Identifies Dysregulation of Hemoglobin and Iron Metabolism in Parkinson’ Disease

Santiago

Potashkin

2017

Front. Aging Neurosci.

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Disrupted iron metabolism has been implicated in the pathogenesis of Parkinson’s disease (PD), a progressive neurodegenerative disorder that severely affects movement and coordination, yet the molecular mechanisms underlying this association remain unknown. To this end, we performed a transcriptomic meta-analysis of four blood microarrays in PD. We observed a significant downregulation of genes related to hemoglobin including, hemoglobin delta (HBD), alpha hemoglobin stabilizing protein (ASHP), genes implicated in iron metabolism including, solute carrier family 11 member 2 (SLC11A2), ferrochelatase (FECH), and erythrocyte-specific genes including erythrocyte membrane protein (EPB42), and 5′-aminolevulinate synthase 2 (ALAS2). Pathway and network analysis identified enrichment in processes related to mitochondrial membrane, oxygen transport, oxygen and heme binding, hemoglobin complex, erythrocyte development, tetrapyrrole metabolism and the spliceosome. Collectively, we identified a subnetwork of genes in blood that may provide a molecular explanation for the disrupted hemoglobin and iron metabolism in the pathogenesis of PD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Blood Transcriptomic Meta-analysis Identifies Dysregulation of Hemoglobin and Iron Metabolism in Parkinson’ Disease

Santiago

Potashkin

2017

Front. Aging Neurosci.

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“…Overexpression of mutant α-synuclein significantly alters the levels of the proteins involved in vesicular traffic and exocytosis (reduced quantities of rabfilin 3A, syntaxin, kinesins 1A, 1B, 2A, increased levels of dynein, dynactin 1) in the substantia nigra and the striatum [82]. A significant reduction in transcript levels (dynamin 2, AP-2, syntaxin-2, VAMP A, VAMP 4), implicated in vesicular cycling, was detected in the peripheral blood of patients at the first stage of PD [84]. …”

Section: Parkinson’s Disease (Pd)mentioning

confidence: 99%

Cholesterol in the Pathogenesis of Alzheimer’s, Parkinson’s Diseases and Autism: Link to Synaptic Dysfunction

2017

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In our previous review, we described brain cholesterol metabolism in control conditions and in the case of some rare neurological pathologies linked to defects in the genes which are directly involved in the synthesis and/or traffic of cholesterol. Here, we have analyzed disruptions in cholesterol homeostasis in widespread neurodegenerative diseases (Alzheimer’s and Parkinson’s diseases) and autism spectrum disorders. We particularly focused on the synaptic dysfunctions that could arise from changes in both membrane cholesterol availability and oxysterol production. Notably, alterations in the brain cholesterol metabolism and neurotransmission occur in the early stages of these pathologies and the polymorphism of the genes associated with cholesterol homeostasis and synaptic communication affects the risk of onset and severity of these diseases. In addition, pharmacological and genetic manipulations of brain cholesterol homeostasis in animal models frequently have marked effects on the progression of neurodegenerative diseases. Thus, the development of Alzheimer’s, Parkinson’s and autism spectrum disorders may be partially associated with an imbalance of cholesterol homeostasis that leads to changes in the membrane cholesterol and oxysterol levels that, in turn, modulates key steps in the synaptic transmission.

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“…With high‐throughput genetic analysis, the emergence of gene expression profiles has became an effective method to identify differentially expressed genes (DEGs) in a variety of diseases which help to explore pathogenesis and develop biomarkers(Alieva et al, ; Du, Yang, Tian, Wang, & He, ; Kong et al, ). Due to differences of samples and platforms in multiple microarray studies, integrated analysis of multiple microarray studies can identify more accurate profiles of DEGs with a larger sample size than a single microarray.…”

Section: Introductionmentioning

confidence: 99%

Identification of key genes and upstream regulators in ischemic stroke

Zhang

Chen

et al. 2019

Brain and Behavior

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Introduction Ischemic stroke (IS) causes severe neurological impairments and physical disabilities and has a high economic burden. Our study aims to identify the key genes and upstream regulators in IS by integrated microarray analysis. Methods An integrated analysis of microarray studies of IS was performed to identify the differentially expressed genes (DEGs) in IS compared to normal control. Based on these DEGs, we performed the functional annotation and transcriptional regulatory network constructions. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was performed to verify the expression of DEGs. Results From two Gene Expression Omnibus datasets obtained, we obtained 1526 DEGs (534 up‐regulated and 992 down‐regulated genes) between IS and normal control. The results of functional annotation showed that Oxidative phosphorylation and Alzheimer's disease were significantly enriched pathways in IS. Top four transcription factors (TFs) with the most downstream genes including PAX4, POU2F1, ELK1, and NKX2‐5. The expression of six genes (ID3, ICAM2, DCTPP1, ANTXR2, DUSP1, and RGS2) was detected by qRT‐PCR. Except for DUSP1 and RGS2, the other four genes in qRT‐PCR played the same pattern with that in our integrated analysis. Conclusions The dysregulation of these six genes may involve with the process of ischemic stroke (IS). Four TFs (PAX4, POU2F1, ELK1 and NKX2‐5) were concluded to play a role in IS. Our finding provided clues for exploring mechanism and developing novel diagnostic and therapeutic strategies for IS.

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Involvement of Endocytosis and Alternative Splicing in the Formation of the Pathological Process in the Early Stages of Parkinson’s Disease

Cited by 30 publications

References 45 publications

Blood Transcriptomic Meta-analysis Identifies Dysregulation of Hemoglobin and Iron Metabolism in Parkinson’ Disease

Blood Transcriptomic Meta-analysis Identifies Dysregulation of Hemoglobin and Iron Metabolism in Parkinson’ Disease

Cholesterol in the Pathogenesis of Alzheimer’s, Parkinson’s Diseases and Autism: Link to Synaptic Dysfunction

Identification of key genes and upstream regulators in ischemic stroke

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