PI3K Signaling in Neurons: A Central Node for the Control of Multiple Functions

Sánchez-Alegría, Karina; Flores-León, Manuel; Ávila-Muñoz, Evangelina; Rodríguez-Corona, Nelly; Arias, Clorinda

doi:10.3390/ijms19123725

Cited by 126 publications

(88 citation statements)

References 114 publications

(135 reference statements)

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“…[106][107][108][109] Besides neurotrophin signaling, interestingly, the pathway-based analysis revealed that these miRNAs act on pathways known to be altered in ischemic conditions and involved in neuroprotection, such as TNF, Hippo, and PI3K. [110][111][112] Among the miRNAs targets here identified, supposed to be downregulated in our model, we highlighted several genes involved in apoptosis and inflammation processes.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of human amniotic fluid stem cells-derived secretome in an ischemia/reperfusion model

Castelli

Antonucci

Tessitore

et al. 2020

Stem Cells Translational Medicine

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Stem cells offer the basis for the promotion of robust new therapeutic approaches for a variety of human disorders. There are still many limitations to be overcome before clinical therapeutic application, including a better understanding of the mechanism by which stem cell therapies may lead to enhanced recovery. In vitro investigations are necessary to dissect the mechanisms involved and to support the potential development in stem cell-based therapies. In spite of growing interest in human amniotic fluid stem cells, not much is known about the characteristics of their secretome and regarding the potential neuroprotective mechanism in different pathologies, including stroke. To get more insight on amniotic fluid cells therapeutic potential, signal transduction pathways activated by human amniotic fluid stem cells (hAFSCs)derived secretome in a stroke in vitro model (ischemia/reperfusion [I/R] model) were investigated by Western blot. Moreover, miRNA expression in the exosomal fraction of the conditioned medium was analyzed. hAFSCs-derived secretome was able to activate prosurvival and anti-apoptotic pathways. MicroRNA analysis in the exosomal component revealed a panel of 16 overexpressed miRNAs involved in the regulation of coherent signaling pathways. In particular, the pathways of relevance in ischemia/reperfusion, such as neurotrophin signaling, and those related to neuroprotection and neuronal cell death, were analyzed. The results obtained strongly point toward the neuroprotective effects of the hAFSCs-conditioned medium in the in vitro stroke model here analyzed. This can be achieved by the modulation and activation of pro-survival processes, at least in part, due to the activity of secreted miRNAs.

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Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of human amniotic fluid stem cells-derived secretome in an ischemia/reperfusion model

Castelli

Antonucci

Tessitore

et al. 2020

Stem Cells Translational Medicine

View full text Add to dashboard Cite

show abstract

“…Xu et al 7 also found that ECM-receptor interaction, protein digestion and absorption, focal adhesion and PI3K-Akt signaling pathway were significantly enriched in the hippocampus of Al-treated rats. Among these pathways, the PI3K-Akt signaling pathway is expressed during central nervous system development 39 and it is well known that this pathway is particularly important for mediating neuronal survival, differentiation and metabolism 40 . In addition, focal adhesion and ECM-receptor interaction signalling are known to be involved in the regulation of synaptic plasticity 7,41 and NF-κB pathway plays a crucial role on neurogenesis, cellular responses to neurological injury and neuroinflammation 42,43 .…”

Section: Discussionmentioning

confidence: 99%

Whole transcriptome approach to evaluate the effect of aluminium hydroxide in ovine encephalon

Varela-Martínez

Bilbao-Arribas

Abendaño

et al. 2020

Sci Rep

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Aluminium hydroxide adjuvants are crucial for livestock and human vaccines. Few studies have analysed their effect on the central nervous system in vivo. In this work, lambs received three different treatments of parallel subcutaneous inoculations during 16 months with aluminium-containing commercial vaccines, an equivalent dose of aluminium hydroxide or mock injections. Brain samples were sequenced by RNA-seq and miRNA-seq for the expression analysis of mRNAs, long non-coding RNAs and microRNAs and three expression comparisons were made. Although few differentially expressed genes were identified, some dysregulated genes by aluminium hydroxide alone were linked to neurological functions, the lncRNA TUNA among them, or were enriched in mitochondrial energy metabolism related functions. In the same way, the miRNA expression was mainly disrupted by the adjuvant alone treatment. Some differentially expressed miRNAs had been previously linked to neurological diseases, oxidative stress and apoptosis. In brief, in this study aluminium hydroxide alone altered the transcriptome of the encephalon to a higher degree than commercial vaccines that present a milder effect. The expression changes in the animals inoculated with aluminium hydroxide suggest mitochondrial disfunction. Further research is needed to elucidate to which extent these changes could have pathological consequences.

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“…The concomitant pathway to Wnt, mTOR, was also implicated in ADHD pathophysiology given that the complex Akt/mTOR-signaling is implicated in cell survival, synaptic plasticity, and formation, neurogenesis, and memory consolidation 84 . Several mutations in participating proteins on this pathway-for example, TSC1/2, RHEB, phosphatase tensin homolog (PTEN), and neurofibromin (NF1)-were described to be implicated with neurological disorders such as ASD, epilepsy, and ADHD 85 .…”

Section: Methylphenidate Treatment and Its Link To Wnt/mtorsignalingmentioning

confidence: 99%

The stress–Wnt-signaling axis: a hypothesis for attention-deficit hyperactivity disorder and therapy approaches

et al. 2020

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Attention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric neurodevelopmental disorders in children and adolescents. Although ADHD has been studied for nearly a century, the cause and pathophysiology of ADHD is yet largely unknown. However, findings from previous studies have resulted in the formation of a new hypothesis: Apart from the well-known multifactorial etiology of ADHD, recent evidence suggests that the interaction between genetic and environmental factors and especially Wnt- and mTOR-signaling pathways might have an important role in the pathophysiology of ADHD. The Wnt-signaling pathway is known to orchestrate cellular proliferation, polarity, and differentiation, and the mTOR pathway is involved in several significant processes of neurodevelopment and synaptic plasticity. As a result, dysregulations of these pathways in a time-dependent manner could lead to neurodevelopmental delays, resulting in ADHD phenotype. This review presents further evidence supporting our hypothesis by combining results from studies on ADHD and Wnt- or mTOR-signaling and the influence of genetics, methylphenidate treatment, Omega-3 supplementation, and stress.

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PI3K Signaling in Neurons: A Central Node for the Control of Multiple Functions

Cited by 126 publications

References 114 publications

Neuroprotective effects of human amniotic fluid stem cells-derived secretome in an ischemia/reperfusion model

Neuroprotective effects of human amniotic fluid stem cells-derived secretome in an ischemia/reperfusion model

Whole transcriptome approach to evaluate the effect of aluminium hydroxide in ovine encephalon

The stress–Wnt-signaling axis: a hypothesis for attention-deficit hyperactivity disorder and therapy approaches

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