Astrocytic MicroRNAs and Transcription Factors in Alzheimer’s Disease and Therapeutic Interventions

Nassar, Ajmal; Kodi, Triveni; Satarker, Sairaj; Gurram, Prasada Chowdari; Upadhya, Dinesh; SM, Fayaz; Mudgal, Jayesh; Nampoothiri, Madhavan

doi:10.3390/cells11244111

Cited by 13 publications

(2 citation statements)

References 202 publications

(241 reference statements)

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“…This emerging field holds great promise in shedding light on the toxicological mechanisms underlying pollutant exposure. Specifically, a mounting body of evidence suggests that miRNAs play a crucial role in a complex regulatory network, not only in the regulation of downstream target genes but also in their own regulation by upstream genes, transcription factors, and epigenetic inheritance (Nassar et al., 2022; Tumolo et al., 2022; Wang et al., 2022). MiRNA is transcribed by RNA polymerase II to generate pri‐miRNA, a process that is subject to regulation by multiple transcription factors.…”

Section: Discussionmentioning

confidence: 99%

NF‐κB1 promotes miR‐27a‐5p upregulation in acrylamide‐induced toxicity in rats

Zhang,

Yang,

Gao

et al. 2024

Food Frontiers

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Acrylamide (AA) is a neurotoxic and potentially carcinogenic contaminant, usually generated during food processing. MicroRNAs are a class of noncoding small RNAs, which serve essential pathogenic roles in linking exposure to toxic contaminants with their pathological outcomes. Our previous research identified miR‐27a‐5p as a key regulator in AA toxicity, as it induces mitochondria‐dependent apoptosis by targeting Btf3 in rats. However, the mechanisms by which miR‐27a‐5p is regulated to exert its toxic effects remain unclear. Here, the transcription factors that bind to the promoter of miR‐27a‐5p and their potential regulatory functions are investigated in cell lines and rats. The results showed that nuclear factor kappa‐B 1 (NF‐κB1) is a promising transcription factor from bioinformatic analysis. The luciferase reporter assay demonstrated that NF‐κB1 enhances the transcriptional activity of the miR‐27a‐5p promoter, whereas the cleavage under targets and tagmentation assay successfully verified the specific binding sites at −305/−298 bp. Furthermore, the inhibition of NF‐κB1 resulted in the suppression of miR‐27a‐5p expression and its associated target pathways, with additional validation provided by in vivo experimentation. Consequently, the upregulation of miR‐27a‐5p induced by AA and its subsequent intrinsic apoptosis can be attributed to the binding of NF‐κB1 to the miR‐27a‐5p promoter. This binding event may serve as the initial step in the molecular network regulated by miR‐27a‐5p that underlies AA toxicity.

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Section: Discussionmentioning

confidence: 99%

NF‐κB1 promotes miR‐27a‐5p upregulation in acrylamide‐induced toxicity in rats

Zhang,

Yang,

Gao

et al. 2024

Food Frontiers

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“…ncRNAs include dicer-dependent microRNAs (miRNA) and short-interfering RNAs (siRNA), shaped by RNA interference pathways [ 42 ]. Literature suggests the presence of microRNAs in astrocytes that regulate glutamatergic and inflammatory signaling, which affect synaptic plasticity [ 43 ]. siRNAs include nucleotides less than thirty in number, while long non-coding RNAs (lncRNA) include more than two hundred nucleotides [ 44 ].…”

Section: Epigeneticsmentioning

confidence: 99%

Epigenetic Alterations in Alzheimer’s Disease: Impact on Insulin Signaling and Advanced Drug Delivery Systems

Greeny,

Nair,

Sadanandan

et al. 2024

Biology

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Alzheimer’s disease (AD) is a neurodegenerative condition that predominantly affects the hippocampus and the entorhinal complex, leading to memory lapse and cognitive impairment. This can have a negative impact on an individual’s behavior, speech, and ability to navigate their surroundings. AD is one of the principal causes of dementia. One of the most accepted theories in AD, the amyloid β (Aβ) hypothesis, assumes that the buildup of the peptide Aβ is the root cause of AD. Impaired insulin signaling in the periphery and central nervous system has been considered to have an effect on the pathophysiology of AD. Further, researchers have shifted their focus to epigenetic mechanisms that are responsible for dysregulating major biochemical pathways and intracellular signaling processes responsible for directly or indirectly causing AD. The prime epigenetic mechanisms encompass DNA methylation, histone modifications, and non-coding RNA, and are majorly responsible for impairing insulin signaling both centrally and peripherally, thus leading to AD. In this review, we provide insights into the major epigenetic mechanisms involved in causing AD, such as DNA methylation and histone deacetylation. We decipher how the mechanisms alter peripheral insulin signaling and brain insulin signaling, leading to AD pathophysiology. In addition, this review also discusses the need for newer drug delivery systems for the targeted delivery of epigenetic drugs and explores targeted drug delivery systems such as nanoparticles, vesicular systems, networks, and other nano formulations in AD. Further, this review also sheds light on the future approaches used for epigenetic drug delivery.

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