Precision Medicine in Neurodegenerative Diseases: Some Promising Tips Coming from the microRNAs’ World

Nuzziello, Nicoletta; Ciaccia, Loredana; Liguori, Maria

doi:10.3390/cells9010075

Cited by 10 publications

(4 citation statements)

References 107 publications

(147 reference statements)

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“…In the last few years, circulating miRNAs have been proposed as potential diagnostic and prognostic biomarkers or even as therapeutic targets for various diseases, including CNS disorders like MS [ 6 , 17 , 72 , 73 ]. The let-7 family regulates many target mRNAs by participating in crucial processes for MS pathophysiology (neuronal homeostasis [ 17 , 24 , 25 ], inflammation [ 1 , 17 ] and miRNA metabolism [ 5 , 26 , 27 ], as in Figure 1 B,B’).…”

Section: Discussionmentioning

confidence: 99%

The microRNA let-7b-5p Is Negatively Associated with Inflammation and Disease Severity in Multiple Sclerosis

Mandolesi

Rizzo

Balletta

et al. 2021

Cells

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The identification of microRNAs in biological fluids for diagnosis and prognosis is receiving great attention in the field of multiple sclerosis (MS) research but it is still in its infancy. In the present study, we observed in a large sample of MS patients that let-7b-5p levels in the cerebrospinal fluid (CSF) were highly correlated with a number of microRNAs implicated in MS, as well as with a variety of inflammation-related protein factors, showing specific expression patterns coherent with let-7b-5p-mediated regulation. Additionally, we found that the CSF let-7b-5p levels were significantly reduced in patients with the progressive MS compared to patients with relapsing-remitting MS and were negatively correlated with characteristic hallmark processes of the two phases of the disease. Indeed, in the non-progressive phase, let-7b-5p inversely associated with both central and peripheral inflammation; whereas, in progressive MS, the CSF levels of let-7b-5p negatively correlated with clinical disability at disease onset and after a follow-up period. Overall, our results uncovered, by the means of a multidisciplinary approach and multiple statistical analyses, a new possible pleiotropic action of let-7b-5p in MS, with potential utility as a biomarker of MS course.

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Section: Discussionmentioning

confidence: 99%

The microRNA let-7b-5p Is Negatively Associated with Inflammation and Disease Severity in Multiple Sclerosis

Mandolesi

Rizzo

Balletta

et al. 2021

Cells

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“…The identification of miRNAs dysregulated in neurodegenerative diseases and construction of related animal models may thus aid in delineation of molecular mechanisms underlying their pathologic processes ( Juzwik et al, 2019 ). Moreover, exploitation of these molecular pathways via precision therapy strategies for neurodegenerative diseases is well underway ( Junn and Mouradian, 2012 ; Pereira et al, 2017 ; Nuzziello et al, 2019 ). While piRNAs have a well-established role in the protection of the germline genome, they also function in somatic cells including neurons ( Lee et al, 2011 ; Yan et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of MicroRNAs and PIWI-Interacting RNAs in a Caenorhabditis elegans Parkinson’s Disease Model Overexpressing Human α-Synuclein and Influence of tdp-1

Shen¹,

Wang

Chen

et al. 2021

Front. Neurosci.

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MicroRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) regulate gene expression and biological processes through specific genetic and epigenetic mechanisms. Recent studies have described a dysregulation of small non-coding RNAs in Parkinson’s disease (PD) tissues but have been limited in scope. Here, we extend these studies by comparing the dysregulation of both miRNAs and piRNAs from transgenic Caenorhabditis elegans (C. elegans) nematodes overexpressing pan-neuronally human α-synuclein wild-type (WT) (HASNWT OX) or mutant (HASNA53T OX). We observed 32 miRNAs and 112 piRNAs dysregulated in HASNA53T OX compared with WT. Genetic crosses of HASNA53T OX PD animal models with tdp-1 null mutants, the C. elegans ortholog of TDP-43, an RNA-binding protein aggregated in frontal temporal lobar degeneration, improved their behavioral deficits and changed the number of dysregulated miRNAs to 11 and piRNAs to none. Neuronal function-related genes T28F4.5, C34F6.1, C05C10.3, camt-1, and F54D10.3 were predicted to be targeted by cel-miR-1018, cel-miR-355-5p (C34F6.1 and C05C10.3), cel-miR-800-3p, and 21ur-1581 accordingly. This study provides a molecular landscape of small non-coding RNA dysregulation in an animal model that provides insight into the epigenetic changes, molecular processes, and interactions that occur during PD-associated neurodegenerative disorders.

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“…Recent progress related to microRNA (miRNA) pharmaco-epigenomics, defined as the use of drugs to treat epigenetic defects connected to a disease, offers new strategies for the development of more effective treatments [82]. The implication of miRNAs in several brain disorders has, indeed, been extensively studied and many authors reported evidence of drug response regulated by miRNA-mediated mechanisms.…”

Section: Neurodegenerative Diseasesmentioning

confidence: 99%

Precision and Personalized Medicine: How Genomic Approach Improves the Management of Cardiovascular and Neurodegenerative Disease

Strianese

Rizzo

Ciccarelli

et al. 2020

Genes

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Life expectancy has gradually grown over the last century. This has deeply affected healthcare costs, since the growth of an aging population is correlated to the increasing burden of chronic diseases. This represents the interesting challenge of how to manage patients with chronic diseases in order to improve health care budgets. Effective primary prevention could represent a promising route. To this end, precision, together with personalized medicine, are useful instruments in order to investigate pathological processes before the appearance of clinical symptoms and to guide physicians to choose a targeted therapy to manage the patient. Cardiovascular and neurodegenerative diseases represent suitable models for taking full advantage of precision medicine technologies applied to all stages of disease development. The availability of high technology incorporating artificial intelligence and advancement progress made in the field of biomedical research have been substantial to understand how genes, epigenetic modifications, aging, nutrition, drugs, microbiome and other environmental factors can impact health and chronic disorders. The aim of the present review is to address how precision and personalized medicine can bring greater clarity to the clinical and biological complexity of these types of disorders associated with high mortality, involving tremendous health care costs, by describing in detail the methods that can be applied. This might offer precious tools for preventive strategies and possible clues on the evolution of the disease and could help in predicting morbidity, mortality and detecting chronic disease indicators much earlier in the disease course. This, of course, will have a major effect on both improving the quality of care and quality of life of the patients and reducing time efforts and healthcare costs.

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Precision Medicine in Neurodegenerative Diseases: Some Promising Tips Coming from the microRNAs’ World

Cited by 10 publications

References 107 publications

The microRNA let-7b-5p Is Negatively Associated with Inflammation and Disease Severity in Multiple Sclerosis

The microRNA let-7b-5p Is Negatively Associated with Inflammation and Disease Severity in Multiple Sclerosis

Dysregulation of MicroRNAs and PIWI-Interacting RNAs in a Caenorhabditis elegans Parkinson’s Disease Model Overexpressing Human α-Synuclein and Influence of tdp-1

Precision and Personalized Medicine: How Genomic Approach Improves the Management of Cardiovascular and Neurodegenerative Disease

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