Extracellular Vesicles, Stem Cells and the Role of miRNAs in Neurodegeneration

Belkozhayev, A.M.; Al-Yozbaki, Minnatallah; George, Alex; Niyazova, Raigul; Sharipov, Kamalidin; Byrne, Lee J.; Wilson, Cornelia M.

doi:10.2174/1570159x19666210817150141

Cited by 10 publications

(3 citation statements)

References 378 publications

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“…One emerging therapeutic approach related to EVs is the use of stem cell-derived EVs. These EVs have a positive impact on the pathophysiology of various neurodegenerative diseases [ 334 ]. In ALS, these EVs may achieve beneficial effects by modulating the immune system, addressing mitochondrial dysfunction, and boosting neuroprotection in MNs [ 335 , 336 , 337 ].…”

Section: Therapeutic Perspectives With Evs In Alsmentioning

confidence: 99%

Recent Advances in Extracellular Vesicles in Amyotrophic Lateral Sclerosis and Emergent Perspectives

Afonso

Cavaleiro

Valero

et al. 2023

Cells

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Amyotrophic lateral sclerosis (ALS) is a severe and incurable neurodegenerative disease characterized by the progressive death of motor neurons, leading to paralysis and death. It is a rare disease characterized by high patient-to-patient heterogeneity, which makes its study arduous and complex. Extracellular vesicles (EVs) have emerged as important players in the development of ALS. Thus, ALS phenotype-expressing cells can spread their abnormal bioactive cargo through the secretion of EVs, even in distant tissues. Importantly, owing to their nature and composition, EVs’ formation and cargo can be exploited for better comprehension of this elusive disease and identification of novel biomarkers, as well as for potential therapeutic applications, such as those based on stem cell-derived exosomes. This review highlights recent advances in the identification of the role of EVs in ALS etiopathology and how EVs can be promising new therapeutic strategies.

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Section: Therapeutic Perspectives With Evs In Alsmentioning

confidence: 99%

Recent Advances in Extracellular Vesicles in Amyotrophic Lateral Sclerosis and Emergent Perspectives

Afonso

Cavaleiro

Valero

et al. 2023

Cells

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“…Stem cells from human milk contain both genetic material and bioactive molecules, such as microRNAs, which can act as epigenetic regulators [ 83 ]. The beneficial effects of breast milk stem cells may also be mediated through the paracrine action of exosomes released by these cells [ 84 , 85 ].…”

Section: Stem Cellsmentioning

confidence: 99%

Potential Epigenetic Effects of Human Milk on Infants’ Neurodevelopment

Gialeli,

Panagopoulou,

Liosis

et al. 2023

Nutrients

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The advantages of human milk feeding, especially in preterm babies, are well recognized. Infants’ feeding with breast milk lowers the likelihood of developing a diverse range of non-communicable diseases later in life and it is also associated with improved neurodevelopmental outcomes. Although the precise mechanisms through which human milk feeding is linked with infants’ neurodevelopment are still unknown, potential epigenetic effects of breast milk through its bioactive components, including non-coding RNAs, stem cells and microbiome, could at least partly explain this association. Micro- and long-non-coding RNAs, enclosed in milk exosomes, as well as breast milk stem cells, survive digestion, reach the circulation and can cross the blood–brain barrier. Certain non-coding RNAs potentially regulate genes implicated in brain development and function, whereas nestin-positive stem cells can possibly differentiate into neural cells or/and act as epigenetic regulators in the brain. Furthermore, breast milk microbiota contributes to the establishment of infant’s gut microbiome, which is implicated in brain development via epigenetic modifications and key molecules’ regulation. This narrative review provides an updated analysis of the relationship between breast milk feeding and infants’ neurodevelopment via epigenetics, pointing out how breast milk’s bioactive components could have an impact on the neurodevelopment of both full-term and preterm babies.

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“…The expansion of CAG trinucleotide repeats located in the coding sequence (CDS) of various human genes is associated with the development of neurodegenerative disorders (NDs), including Huntington’s disease (HD) ( Paulson, 2018 ; Ciosi et al, 2021 ). HD is an inherited pathology ND of the nervous system, which is caused by the abnormal expansion of a CAG trinucleotide repeat (>35 repeats) in the HTT gene on chromosome 4р16.3 ( Belkozhayev A. M. et al, 2022 ). In patients, it is characterized by involuntary chorei movements, behavioral, and psychiatric disorders, including dementia ( Roos, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Differential microRNA expression in the SH-SY5Y human cell model as potential biomarkers for Huntington’s disease

Belkozhayev,

Niyazova,

Kamal

et al. 2024

Front. Cell. Neurosci.

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Huntington’s disease (HD) is caused by an expansion of CAG trinucleotide repeat in the HTT gene; the exact pathogenesis of HD currently remains unclear. One of the promising directions in the study of HDs is to determine the molecular mechanism underlying the development and role of microRNAs (miRNAs). This study aimed to identify the profile of miRNAs in an HD human cell line model as diagnostic biomarkers for HD. To study HD, the human SH-SY5Y HD cell model is based on the expression of two different forms: pEGFP-Q23 and pEGFP-Q74 of HTT. The expression of Htt protein was confirmed using aggregation assays combined with immunofluorescence and Western blotting methods. miRNA levels were measured in SH-SY5Y neuronal cell model samples stably expressing Q23 and Q74 using the extraction-free HTG EdgeSeq protocol. A total of 2083 miRNAs were detected, and 354 (top 18 miRNAs) miRNAs were significantly differentially expressed (DE) (p < 0.05) in Q23 and Q74 cell lines. A majority of the miRNAs were downregulated in the HD cell model. Moreover, we revealed that six DE miRNAs target seven genes (ATN1, GEMIN4, EFNA5, CSMD2, CREBBP, ATXN1, and B3GNT) that play important roles in neurodegenerative disorders and showed significant expression differences in mutant Htt (Q74) when compared to wild-type Htt (Q23) using RT-qPCR (p < 0.05 and 0.01). We demonstrated the most important DE miRNA-mRNA profiles, interaction binding sites, and their related pathways in HD using experimental and bioinformatics methods. This will allow the development of novel diagnostic strategies and provide alternative therapeutic routes for treating HD.

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Extracellular Vesicles, Stem Cells and the Role of miRNAs in Neurodegeneration

Cited by 10 publications

References 378 publications

Recent Advances in Extracellular Vesicles in Amyotrophic Lateral Sclerosis and Emergent Perspectives

Recent Advances in Extracellular Vesicles in Amyotrophic Lateral Sclerosis and Emergent Perspectives

Potential Epigenetic Effects of Human Milk on Infants’ Neurodevelopment

Differential microRNA expression in the SH-SY5Y human cell model as potential biomarkers for Huntington’s disease

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