Genome‐wide data mining to construct a competing endogenous RNA network and reveal the pivotal therapeutic targets of Parkinson's disease

Zhang, Jing; Chen, Ruiying; Shi, Fan; Yang, Pan Chyr; Sun, Kun; Yang, Xiaojing; Jin, Yulan

doi:10.1111/jcmm.16190

Cited by 8 publications

(3 citation statements)

References 38 publications

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“…A recent proteomic study of the amygdala from Parkinson’s disease brains indicates that there may be some measures in place to protect the balance of synaptic proteins in the amygdala complex of PD patients. Compared to controls, PD amygdala showed upregulation of NPTN, which has been reported in induction of neurite outgrowth and regulation of synaptic structure, function and plasticity (Beesley et al, 2014; Villar-Conde et al, 2023; J. Zhang et al, 2021; Zhang et al, 2022).…”

Section: Discussionmentioning

confidence: 89%

Cortico-amygdala synaptic structural abnormalities produced by templated aggregation of α-synuclein

Gcwensa,

Russell,

Long

et al. 2024

Preprint

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Parkinsons disease (PD) and Dementia with Lewy bodies (DLB) are characterized by neuronal α-synuclein (α-syn) inclusions termed Lewy Pathology, which are abundant in the amygdala. The basolateral amygdala (BLA), in particular, receives projections from the thalamus and cortex. These projections play a role in cognition and emotional processing, behaviors which are impaired in α-synucleinopathies. To understand if and how pathologic α-syn impacts the BLA requires animal models of α-syn aggregation. Injection of α-synuclein pre-formed fibrils (PFFs) into the striatum induces robust α-synuclein aggregation in excitatory neurons in the BLA that corresponds with reduced contextual fear conditioning. At early time points after aggregate formation, cortico-amygdala excitatory transmission is abolished. The goal of this project was to determine if α-syn inclusions in the BLA induce synaptic degeneration and/or morphological changes. In this study, we used C57BL/6J mice injected bilaterally with PFFs in the dorsal striatum to induce α-syn aggregate formation in the BLA. A method was developed using immunofluorescence and three-dimensional reconstruction to analyze excitatory cortico-amygdala and thalamo-amygdala presynaptic terminals closely juxtaposed to postsynaptic densities. The abundance and morphology of synapses were analyzed at 6- or 12-weeks post-injection of PFFs. α-Syn aggregate formation in the BLA did not cause a significant loss of synapses, but cortico-amygdala and thalamo-amygdala presynaptic terminals and postsynaptic densities with aggregates of α-synuclein show increased volumes, similar to previous findings in human DLB cortex, and in non-human primate models of PD. Transmission electron microscopy showed that PFF-injected mice showed reduced intervesicular distances similar to a recent study showing phospho-serine-129 α-synuclein increases synaptic vesicle clustering. Thus, pathologic α-synuclein causes major alterations to synaptic architecture in the BLA, potentially contributing to behavioral impairment and amygdala dysfunction observed in synucleinopathies.

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Section: Discussionmentioning

confidence: 89%

Cortico-amygdala synaptic structural abnormalities produced by templated aggregation of α-synuclein

Gcwensa,

Russell,

Long

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…The HoxB3 was identified as a potential biomarker for osteoarthritis [ 37 ] and might be used for the prediction of clinically isolated syndrome progress to relapsing-remitting multiple sclerosis [ 38 , 39 ]. The aberrant expression of HoxB3 might promote Parkinson’s disease via dysregulating sphingolipid and glutathione metabolism [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Investigation of HoxB3 and Growth Factors Expression in Placentas of Various Gestational Ages

Kreicberga

Junga

Pilmane

2021

JDB

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An evaluation of transforming growth factor beta (TGFβ), hepatocyte growth factor (HGF), basic fibroblast growth factor (FGF-2), fibroblast growth factors receptor 1 (FGFR1) and Hox-positive cells in the human placenta, and their correlation with gestational time at delivery and pregnancy outcomes, may provide not only a better understanding of the role of Hox genes and growth factors in human development, but also may be of clinical importance in reproductive medicine. This study analyzed the immunohistochemical identification of TGFβ, HGF, FGF-2, FGFR1 and HoxB3 in placentas of various gestational ages. We found few (+) TGFβ, moderate (++) FGF-2 and numerous (+++) HGF and FGFR1 positive structures. Occasional (0/+) to numerous (+++) HoxB3-positive structures were detected in different types of placental cells specifically, cytotrophoblasts, syncytiotrophoblast, extravillous trophoblasts, and Höfbauer cells. Correlating the appearance of HoxB3 staining in placentas with neonatal parameters, we found a statistically significant negative correlation with ponderal index (r = −0.323, p = 0.018) and positive correlation with neonate body length (r = 0.541, p = 0.046). The number of HoxB3-positive cells did not correlate with growth factors and gestational age, but with neonatal anthropometrical parameters, indicating the role of HoxB3 not only in placental development, but also in the longitudinal growth of the fetus. TGFβ and FGF-2 did not play a significant role in the development of the placenta beyond 22nd week of pregnancy, while HGF and FGFR1 immunoreactive cells increased with advancing gestation, indicating increasingly evolving maturation (growth, proliferation) of the placenta, especially in the third trimester.

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“…On the other hand, only a few studies investigate the miRNA sponging in neurodegenerative and NPDs. These studies are restricted to inferring ceRNA primarily based on differential expressed lncRNAs and mRNA (Zhou et al, 2019 ; Zhang X. et al, 2020 , Zhang J. et al, 2021 ; Zhang Y. et al, 2021 ; He et al, 2021 ; Sabaie et al, 2021a , b ). There is a need to infer miRNA sponge modules by considering the expression of miRNA, lncRNAs, and mRNA.…”

Section: Introductionmentioning

confidence: 99%

Inferring miRNA sponge modules across major neuropsychiatric disorders

Balasubramanian

Vinod²

2022

Front. Mol. Neurosci.

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The role of non-coding RNAs in neuropsychiatric disorders (NPDs) is an emerging field of study. The long non-coding RNAs (lncRNAs) are shown to sponge the microRNAs (miRNAs) from interacting with their target mRNAs. Investigating the sponge activity of lncRNAs in NPDs will provide further insights into biological mechanisms and help identify disease biomarkers. In this study, a large-scale inference of the lncRNA-related miRNA sponge network of pan-neuropsychiatric disorders, including autism spectrum disorder (ASD), schizophrenia (SCZ), and bipolar disorder (BD), was carried out using brain transcriptomic (RNA-Seq) data. The candidate miRNA sponge modules were identified based on the co-expression pattern of non-coding RNAs, sharing of miRNA binding sites, and sensitivity canonical correlation. miRNA sponge modules are associated with chemical synaptic transmission, nervous system development, metabolism, immune system response, ribosomes, and pathways in cancer. The identified modules showed similar and distinct gene expression patterns depending on the neuropsychiatric condition. The preservation of miRNA sponge modules was shown in the independent brain and blood-transcriptomic datasets of NPDs. We also identified miRNA sponging lncRNAs that may be potential diagnostic biomarkers for NPDs. Our study provides a comprehensive resource on miRNA sponging in NPDs.

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Genome‐wide data mining to construct a competing endogenous RNA network and reveal the pivotal therapeutic targets of Parkinson's disease

Cited by 8 publications

References 38 publications

Cortico-amygdala synaptic structural abnormalities produced by templated aggregation of α-synuclein

Cortico-amygdala synaptic structural abnormalities produced by templated aggregation of α-synuclein

Investigation of HoxB3 and Growth Factors Expression in Placentas of Various Gestational Ages

Inferring miRNA sponge modules across major neuropsychiatric disorders

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