MicroRNA Networks in Cognition and Dementia

Abstract

The change from viewing noncoding RNA as “junk” in the genome to seeing it as a critical epigenetic regulator in almost every human condition or disease has forced a paradigm shift in biomedical and clinical research. Small and long noncoding RNA transcripts are now routinely evaluated as putative diagnostic or therapeutic agents. A prominent role for noncoding microRNAs in the central nervous system has uncovered promising new clinical candidates for dementia-related disorders, treatments for which currently remain elusive even as the percentage of diagnosed patients increases significantly. Cognitive decline is a core neurodegenerative process in Alzheimer’s Disease, Frontotemporal Dementia, Lewy body dementia, vascular dementia, Huntington’s Disease, Creutzfeldt–Jakob disease, and a significant portion of Parkinson’s Disease patients. This review will discuss the microRNA-associated networks which influence these pathologies, including inflammatory and viral-mediated pathways (such as the novel SARS-CoV-2 virus implicated in COVID-19), and their current status in clinical trials.

Cognitive dysfunction associated with COVID-19: Prognostic role of circulating biomarkers and microRNAs

“…CNS upregulation of miR-155 has been associated cognitive dysfunction and is the most expressed chromosome 21 miRNA in Down's Syndrome dementia, as it is co-expressed with hyperphosphorylated tau protein (Tili et al, 2018). miR-155 act as a prevalent CNS pro-inflammatory mediator and Ma et al, 2011;Feng et al, 2018;Gao et al, 2020;Bai and Bian, 2022;Blount et al, 2022 Ischemia stroke (IS), Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Multiple sclerosis (MS), Multiple system atrophy (MSA), mild cognitive impairment (MIC), Peripheral blood mononuclear cell (PBMC), interleukin-1 receptor-associated kinase 1 (IRAK1), receptor-associated factor 6 (TRAF6), Suppressor of Cytokine Signaling 1 (SOCS1), SH2 Domain-Containing Inositol 5'-Phosphatase1 (SHIP1), Signal Transducers and Activators of Transcription 5 (STAT5) and IL-13 Receptor Alpha 1 (IL13Ra1), Dedicator of cytokinesis 1 (DOCK-1), toll-like receptor 7 (TLR7), High-mobility group AT-hook 2 (HMGA2), amyloid precursor protein (APP), β-secretase (BACE1), parkin E3 ubiquitinprotein ligase (PARK2), interacting GYF protein 2 (GIGYF2), Ras Homolog Family Member A (RhoA), tubulin associated unit protein (TAU protein), Nuclear factor kappaβ (NF-κβ), Phosphatase and tensin homolog (PTEN), Phosphoinositide 3-kinase (PI3K), Mammalian target of rapamycin complex 1 (mTOR1), Glycogen Synthase Kinase 3 Beta (GSK-3β), toll-like receptor 4 (TLR4).…”

“…Growing evidence suggests that as post-transcriptional regulators of gene expression, miRNAs are involved in physiological and pathological processes and their dysregulation in function is synonymous with a multiplicity of diseases ( Condrat et al, 2020 ; Carini et al, 2021 ). The prominent role of non-coding microRNAs in CNS and their signature in the circulation has been well established in various neurodegenerative diseases ( Thounaojam et al, 2013 ; Bahlakeh et al, 2021 ; Islam et al, 2021c ; Perdoncin et al, 2021 ; Blount et al, 2022 ). Hence, miRNAs as possible therapeutic targets and disease markers for early diagnosis have strongly been advocated because of their stability and convenience in extraction from biological fluids ( Szelenberger et al, 2019 ).…”

“…Microglial miR-21 has been reported to protect neurons from cell death under hypoxic conditions ( Zhang et al, 2012 ). miR-21 has been shown to restore neurogenesis and reverse cellular senescence via inhibition of the mTOR1 pathway in models of vascular dementia, making a candidate as a potential therapeutic in the treatment of vascular dementia and its associated cognitive impairment ( Blount et al, 2022 ).…”

MicroRNA signature of leukocytes in the context of chronic systemic inflammation in vascular dementia

“…Современная точка зрения свидетельствует, что хроническое низкоуровневое воспаление, наблюдаемое в ходе старения организма, выступает ключевым фактором риска активации резидентных клеток врожденной иммунной системы мозга (микроглии и астроцитов), вступающих на путь секреции классических цитокинов воспаления -IL-1β, IL-6, TNFα, внутри мозга. Последующая сверхактивация этих клеток приводит к развитию нейровоспаления, цереброваскулярных нарушений и когнитивной недостаточности, презентация которых является базовым и/или ко-ассоциированными симптомами нейродегенеративных заболеваний (НЗ), таких как болезнь Альцгеймера, сосудистая деменция, болезнь Паркинсона и других [3,4,8,12].…”

MicroRNA-Mediated Silencing Pathways in the Nervous System and Neurological Diseases

“…Campos Pereira updates more recent studies on miRNA deregulation in prion disease, elucidating a translational approach from molecular to miRNA-based therapies, as frontier research in neurodegenerative disease [ 13 ]. Lastly, Blount et al close this Special Issue with a critical review on the topic with a focus on miRNAs involvement in cognitive processes and dementia, mentioning the last suggestion generated by a new clinical frame of COVID-19 and SARS-CoV-2 virus [ 14 ].…”