Genetic Determinants Highlight the Existence of Shared Etiopathogenetic Mechanisms Characterizing Age-Related Macular Degeneration and Neurodegenerative Disorders

Strafella, Claudia; Caputo, Valerio; Termine, Andrea; Fabrizio, Carlo; Ruffo, Paola; Potenza, Saverio; Cusumano, Andrea; Ricci, Federico; Caltagirone, Carlo; Giardina, Emiliano; Cascella, Raffaella

doi:10.3389/fneur.2021.626066

Cited by 10 publications

(9 citation statements)

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“…MicroRNAs (miRNAs) are small oligonucleotide sequences (about 19–22 base pairs) of single-stranded non-coding RNA, which play a crucial function by regulating gene expression at post-transcriptional level ( Figure 1 ). The action of miRNAs has been suggested as a mechanism to regulate neuroinflammation in different NDs including ALS ( Benigni et al, 2016 ; Bai et al, 2017a ; Wang et al, 2020 ; Strafella et al, 2021a ; Strafella et al, 2021b ).…”

Section: Introductionmentioning

confidence: 99%

Deregulation of ncRNA in Neurodegenerative Disease: Focus on circRNA, lncRNA and miRNA in Amyotrophic Lateral Sclerosis

et al. 2021

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Parallel and massive sequencing of total RNA samples derived from different samples are possible thanks to the use of NGS (Next Generation Sequencing) technologies. This allowed characterizing the transcriptomic profile of both cell and tissue populations, increasing the knowledge of the molecular pathological processes of complex diseases, such as neurodegenerative diseases (NDs). Among the NDs, Amyotrophic Lateral Sclerosis (ALS) is caused by the progressive loss of motor neurons (MNs), and, to date, the diagnosis is often made by exclusion because there is no specific symptomatologic picture. For this reason, it is important to search for biomarkers that are clinically useful for carrying out a fast and accurate diagnosis of ALS. Thanks to various studies, it has been possible to propose several molecular mechanisms associated with the disease, some of which include the action of non-coding RNA, including circRNAs, miRNAs, and lncRNAs which will be discussed in the present review. The evidence analyzed in this review highlights the importance of conducting studies to better characterize the different ncRNAs in the disease to use them as possible diagnostic, prognostic, and/or predictive biomarkers of ALS and other NDs.

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Section: Introductionmentioning

confidence: 99%

Deregulation of ncRNA in Neurodegenerative Disease: Focus on circRNA, lncRNA and miRNA in Amyotrophic Lateral Sclerosis

et al. 2021

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“…In addition, the present study highlighted an interaction between miR-146 and miR-155 signaling pathway, which is consistent with literature studies showing their cooperation in the modulation of the microglial inflammatory profile and supporting them as druggable targets for restoring microglial activity in multiple neurodegenerative disorders ( Sierksma et al, 2018 ; Kou et al, 2020 ; Varma-Doyle et al, 2021 ). In this scenario, it is important to include even miR499a and miR-196a2, which have been associated with aMCI in this study and with other complex disorders ( Kiselev et al, 2015 ; Strafella et al, 2021a , b ).…”

Section: Discussionmentioning

confidence: 99%

“…The study was performed utilizing a panel of 120 variants available from two previous studies ( Strafella et al, 2021a , b ) conducted on other complex disorders, which are known to share some disease mechanisms with MCI and AD. The genetic variants of interest have been selected in relation to their location within or nearby genes primarily involved in cellular homeostasis, inflammation, immune response, signal transduction, neuronal development and functioning, synaptogenesis as well as genes known to be involved in AD, MCI and other complex diseases characterized by neurodegeneration (namely, Parkinson’s Disease and Multiple Sclerosis).…”

Section: Methodsmentioning

confidence: 99%

“…The genetic variants of interest have been selected in relation to their location within or nearby genes primarily involved in cellular homeostasis, inflammation, immune response, signal transduction, neuronal development and functioning, synaptogenesis as well as genes known to be involved in AD, MCI and other complex diseases characterized by neurodegeneration (namely, Parkinson's Disease and Multiple Sclerosis). A detailed description of the methods utilized for selecting the variants of interest is available within the referenced paper and its Supplementary Material (Strafella et al, 2021a).…”

Section: Selection Of Genetic Variantsmentioning

confidence: 99%

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Identification of Genetic Networks Reveals Complex Associations and Risk Trajectory Linking Mild Cognitive Impairment to Alzheimer’s Disease

Strafella

Caputo

Termine

et al. 2022

Front. Aging Neurosci.

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Amnestic mild cognitive impairment (aMCI) and sporadic Alzheimer’s disease (AD) are multifactorial conditions resulting from a complex crosstalk among multiple molecular and biological processes. The present study investigates the association of variants localized in genes and miRNAs with aMCI and AD, which may represent susceptibility, prognostic biomarkers or multi-target treatment options for such conditions. We included 371 patients (217 aMCI and 154 AD) and 503 healthy controls, which were genotyped for a panel of 120 single nucleotide polymorphisms (SNPs) and, subsequently, analyzed by statistical, bioinformatics and machine-learning approaches. As a result, 21 SNPs were associated with aMCI and 13 SNPs with sporadic AD. Interestingly, a set of variants shared between aMCI and AD displayed slightly higher Odd Ratios in AD with respect to aMCI, highlighting a specific risk trajectory linking aMCI to AD. Some of the associated genes and miRNAs were shown to interact within the signaling pathways of APP (Amyloid Precursor Protein), ACE2 (Angiotensin Converting Enzyme 2), miR-155 and PPARG (Peroxisome Proliferator Activated Receptor Gamma), which are known to contribute to neuroinflammation and neurodegeneration. Overall, results of this study increase insights concerning the genetic factors contributing to the neuroinflammatory and neurodegenerative mechanisms underlying aMCI and sporadic AD. They have to be exploited to develop personalized approaches based on the individual genetic make-up and multi-target treatments.

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“…It suggests a targetome on miRNAs base, from Integer Linear Program (ILP) development. miRPathDB is linked to other free resources such as miRTarBase, TargetScan, and miRanda [ 115 , 116 ].…”

Section: Overview Of Available Methods For Reconstructing Interactions Between Ncrnas and Other Moleculesmentioning

confidence: 99%

Bioinformatic Tools for the Analysis and Prediction of ncRNA Interactions

Rincón-Riveros

Morales

Rodríguez

et al. 2021

IJMS

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Noncoding RNAs (ncRNAs) play prominent roles in the regulation of gene expression via their interactions with other biological molecules such as proteins and nucleic acids. Although much of our knowledge about how these ncRNAs operate in different biological processes has been obtained from experimental findings, computational biology can also clearly substantially boost this knowledge by suggesting possible novel interactions of these ncRNAs with other molecules. Computational predictions are thus used as an alternative source of new insights through a process of mutual enrichment because the information obtained through experiments continuously feeds through into computational methods. The results of these predictions in turn shed light on possible interactions that are subsequently validated experimentally. This review describes the latest advances in databases, bioinformatic tools, and new in silico strategies that allow the establishment or prediction of biological interactions of ncRNAs, particularly miRNAs and lncRNAs. The ncRNA species described in this work have a special emphasis on those found in humans, but information on ncRNA of other species is also included.

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Genetic Determinants Highlight the Existence of Shared Etiopathogenetic Mechanisms Characterizing Age-Related Macular Degeneration and Neurodegenerative Disorders

Cited by 10 publications

References 51 publications

Deregulation of ncRNA in Neurodegenerative Disease: Focus on circRNA, lncRNA and miRNA in Amyotrophic Lateral Sclerosis

Deregulation of ncRNA in Neurodegenerative Disease: Focus on circRNA, lncRNA and miRNA in Amyotrophic Lateral Sclerosis

Identification of Genetic Networks Reveals Complex Associations and Risk Trajectory Linking Mild Cognitive Impairment to Alzheimer’s Disease

Bioinformatic Tools for the Analysis and Prediction of ncRNA Interactions

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