Abstract:Long noncoding RNAs (lncRNAs) are RNA molecules comprising more than 200 nucleotides, which are not translated into proteins. Many studies have shown that lncRNAs are involved in regulating a variety of biological processes, including immune, cancer, stress, development and differentiation at the transcriptional, epigenetic or post‐transcriptional levels. Here, we review the role of lncRNAs in the process of neurodevelopment, neural differentiation, synaptic function, and pathogenesis of Parkinson's disease (P… Show more
“…Differentially expressed upregulated lncRNAs in long-term VM culture included the well-known nuclear paraspeckle assembly transcript 1 ( NEAT1 ), overexpressed in the substantia nigra, as well as H19 , MALAT1 , and SNHG12 , previously reported to be enriched at early stages of PD pathogenesis ( Figure 6 B,E and Supplementary Table S2 ) [ 26 , 27 , 28 ]. We also found upregulated expression of AC005062.1 and AL590302.1 , as well as LINC02019 and the antisense SPRY4-AS1 , previously associated with tumorigenesis ( Supplementary Figure S3D and Supplementary Table S2 ) [ 29 ].…”
Dopaminergic (DA) neurons derived from human pluripotent stem cells (hPSCs) represent a renewable and available source of cells useful for understanding development, developing disease models, and stem-cell therapies for Parkinson’s disease (PD). To assess the utility of stem cell cultures as an in vitro model system of human DA neurogenesis, we performed high-throughput transcriptional profiling of ~20,000 ventral midbrain (VM)-patterned stem cells at different stages of maturation using droplet-based single-cell RNA sequencing (scRNAseq). Using this dataset, we defined the cellular composition of human VM cultures at different timepoints and found high purity DA progenitor formation at an early stage of differentiation. DA neurons sharing similar molecular identities to those found in authentic DA neurons derived from human fetal VM were the major cell type after two months in culture. We also developed a bioinformatic pipeline that provided a comprehensive long noncoding RNA landscape based on temporal and cell-type specificity, which may contribute to unraveling the intricate regulatory network of coding and noncoding genes in DA neuron differentiation. Our findings serve as a valuable resource to elucidate the molecular steps of development, maturation, and function of human DA neurons, and to identify novel candidate coding and noncoding genes driving specification of progenitors into functionally mature DA neurons.
“…Differentially expressed upregulated lncRNAs in long-term VM culture included the well-known nuclear paraspeckle assembly transcript 1 ( NEAT1 ), overexpressed in the substantia nigra, as well as H19 , MALAT1 , and SNHG12 , previously reported to be enriched at early stages of PD pathogenesis ( Figure 6 B,E and Supplementary Table S2 ) [ 26 , 27 , 28 ]. We also found upregulated expression of AC005062.1 and AL590302.1 , as well as LINC02019 and the antisense SPRY4-AS1 , previously associated with tumorigenesis ( Supplementary Figure S3D and Supplementary Table S2 ) [ 29 ].…”
Dopaminergic (DA) neurons derived from human pluripotent stem cells (hPSCs) represent a renewable and available source of cells useful for understanding development, developing disease models, and stem-cell therapies for Parkinson’s disease (PD). To assess the utility of stem cell cultures as an in vitro model system of human DA neurogenesis, we performed high-throughput transcriptional profiling of ~20,000 ventral midbrain (VM)-patterned stem cells at different stages of maturation using droplet-based single-cell RNA sequencing (scRNAseq). Using this dataset, we defined the cellular composition of human VM cultures at different timepoints and found high purity DA progenitor formation at an early stage of differentiation. DA neurons sharing similar molecular identities to those found in authentic DA neurons derived from human fetal VM were the major cell type after two months in culture. We also developed a bioinformatic pipeline that provided a comprehensive long noncoding RNA landscape based on temporal and cell-type specificity, which may contribute to unraveling the intricate regulatory network of coding and noncoding genes in DA neuron differentiation. Our findings serve as a valuable resource to elucidate the molecular steps of development, maturation, and function of human DA neurons, and to identify novel candidate coding and noncoding genes driving specification of progenitors into functionally mature DA neurons.
“…Accumulating evidences have illuminated that lncRNAs have been participated in disrupting mitochondrial function, regulating α-Syn expression and Lewy body formation, mediating apoptosis, and other mechanisms of PD pathogenesis (Lyu et al, 2019). The lncRNA, NEAT1, regulates the transcription of α-Syn, participates in α-Syn-associated apoptosis (Liu and Lu, 2018), and regulates MPP (+)-induced neuronal injury by targeting miR-124 (Xie et al, 2019).…”
Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by dopaminergic neuron death and the abnormal accumulation and aggregation of α-synuclein (α-Syn) in the substantia nigra (SN). Although the abnormal accumulation of α-Syn can solely promote and accelerate the progress of PD, the underlying molecular mechanisms remain unknown. Mounting evidence confirms that the abnormal expression of long non-coding RNA (lncRNA) plays an important role in PD. Our previous study found that exogenous α-Syn induced the downregulation of lncRNA-T199678 in SH-SY5Y cells via a gene microarray analysis. This finding suggested that lncRNA-T199678 might have a potential pathological role in the pathogenesis of PD. This study aimed to explore the influence of lncRNA-T199678 on α-Syn-induced dopaminergic neuron injury. Overexpression of lncRNA-T199678 ameliorated the neuron injury induced by α-Syn via regulating oxidative stress, cell cycle, and apoptosis. Studies indicate lncRNAs could regulate posttranscriptional gene expression via regulating the downstream microRNA (miRNA). To discover the downstream molecular target of lncRNA-T199678, the following experiment found out that miR-101-3p was a potential target for lncRNA-T199678. Further study showed that the upregulation of lncRNA-T199678 reduced α-Syn-induced neuronal damage through miR-101-3p in SH-SY5Y cells and lncRNA-T199678 was responsible for the α-Syn-induced intracellular oxidative stress, dysfunction of the cell cycle, and apoptosis. All in all, lncRNA-T199678 mitigated the α-Syn-induced dopaminergic neuron injury via targeting miR-101-3p, which contributed to promote PD. Our results highlighted the role of lncRNA-T199678 in mitigating dopaminergic neuron injury in PD and revealed a new molecular target for PD.
“…PD is the second most common neurodegenerative disorder after AD in aging individuals, the main characteristics of which are the progressive loss of dopaminergic neurons in the substantia nigra pars compacta and the formation of Lewy bodies within the cytoplasm, leading to motor dysregulation [ 48 , 49 ]. Although the pathogenesis remains not fully understood, PD is widely assumed to be associated with both genetic and environmental factors [ 35 ].…”
Section: Lncrna As Regulators Of Autophagy In Neurological Diseasementioning
Neurological diseases are a major threat to global public health and prosperity. The number of patients with neurological diseases is increasing due to the population aging and increasing life expectancy. Autophagy is one of the crucial mechanisms to maintain nerve cellular homeostasis. Numerous studies have demonstrated that autophagy plays a dual role in neurological diseases. Long noncoding RNAs (lncRNAs) are a vital class of noncoding RNAs with a length of more than 200 nucleotides and cannot encode proteins themselves but are expressed in most neurological diseases. An early phase, emerging knowledge has revealed that long noncoding RNAs (lncRNAs) are crucial in autophagy regulation. Furthermore, autophagy-associated lncRNAs can promote the development of neurological diseases or slow their progression. In this review, we introduce a general overview of lncRNA functional mechanisms and summarizes the recent progress of lncRNAs on autophagy regulation in neurological diseases to reveal possible novel therapeutic targets or useful biomarkers.
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