Advances and Challenges in Understanding MicroRNA Function in Tauopathies: A Case Study of miR-132/212

Boscher, Emmanuelle; Hernandez-Rapp, Julia; Pétry, Séréna; Keraudren, Rémi; Rainone, Sara; Loiselle, Andréanne; Goupil, Claudia; Turgeon, Andréanne; St‐Amour, Isabelle; Planel, Emmanuel; Hébert, Sébastien S.

doi:10.3389/fneur.2020.578720

Cited by 5 publications

(3 citation statements)

References 90 publications

(138 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies have shown that miR-132-3p is neuroprotective generally [ 21 , 24 , 50 , 51 ] as well as specifically in AD [ 22 , 52 ]. Interrogation of the TargetScan database showed that mRNAs encoding ERK1, ERK2 and TAU are also theoretical targets of miR-132-3p, with similar context++ scores to miR-483-5p.…”

Section: Discussionmentioning

confidence: 99%

Candidate Alzheimer’s Disease Biomarker miR-483-5p Lowers TAU Phosphorylation by Direct ERK1/2 Repression

Nagaraj

Want

Laskowska-Kaszub

et al. 2021

IJMS

View full text Add to dashboard Cite

MicroRNAs have been demonstrated as key regulators of gene expression in the etiology of a range of diseases including Alzheimer’s disease (AD). Recently, we identified miR-483-5p as the most upregulated miRNA amongst a panel of miRNAs in blood plasma specific to prodromal, early-stage Alzheimer’s disease patients. Here, we investigated the functional role of miR-483-5p in AD pathology. Using TargetScan and miRTarBase, we identified the microtubule-associated protein MAPT, often referred to as TAU, and the extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2), known to phosphorylate TAU, as predicted direct targets of miR-483-5p. Employing several functional assays, we found that miR-483-5p regulates ERK1 and ERK2 at both mRNA and protein levels, resulting in lower levels of phosphorylated forms of both kinases. Moreover, miR-483-5p-mediated repression of ERK1/2 resulted in reduced phosphorylation of TAU protein at epitopes associated with TAU neurofibrillary pathology in AD. These results indicate that upregulation of miR-483-5p can decrease phosphorylation of TAU via ERK pathway, representing a compensatory neuroprotective mechanism in AD pathology. This miR-483-5p/ERK1/TAU axis thus represents a novel target for intervention in AD.

show abstract

Section: Discussionmentioning

confidence: 99%

Candidate Alzheimer’s Disease Biomarker miR-483-5p Lowers TAU Phosphorylation by Direct ERK1/2 Repression

Nagaraj

Want

Laskowska-Kaszub

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Despite the discovery of miRNAs representing a potential breakthrough, much remains to be determined regarding their neurobiology, mode of action, mutual interactions, and the ideal means of modulat-ing their activities, to enable the development of potentially valuable therapeutic approaches. 279 Studies in AD brain tissues and Drosophila melanogaster models have found that tau may mediate aberrant activation and mobilization of transposable elements, also known as "jumping genes." 280 Increased retrotransposition of transposable elements, a key mediator of neuronal death, was also found in post mortem brains of subjects with tauopathies.…”

Section: Other Anti-tau Approachesmentioning

confidence: 99%

Section: Anti‐tau Drugsmentioning

confidence: 99%

A critical appraisal of tau‐targeting therapies for primary and secondary tauopathies

Imbimbo

Ippati

Watling

et al. 2021

Alzheimer's & Dementia

View full text Add to dashboard Cite

Introduction: Primary tauopathies are neurological disorders in which tau protein deposition is the predominant pathological feature. Alzheimer's disease is a secondary tauopathy with tau forming hyperphosphorylated insoluble aggregates. Tau pathology can propagate from region to region in the brain, while alterations in tau processing may impair tau physiological functions. Methods:We reviewed literature on tau biology and anti-tau drugs using PubMed, meeting abstracts, and ClnicalTrials.gov. Results:The past 15 years have seen >30 drugs interfering with tau aggregation, processing, and accumulation reaching the clinic. Initial results with tau aggregation inhibitors and anti-tau monoclonal antibodies have not shown clinical efficacy. Discussion:The reasons for these clinical failures are unclear but could be linked to the clearing of physiological forms of tau by non-specific drugs. Research is now concentrating efforts on developing reliable translational animal models and selective compounds targeting specific tau epitopes, neurotoxic tau aggregates, and posttranslational tau modifications.

show abstract

Targeting epigenetics: A novel promise for Alzheimer’s disease treatment

Jeremic

Jiménez‐Díaz

Navarro‐López

2023

Ageing Research Reviews

View full text Add to dashboard Cite

Advances and Challenges in Understanding MicroRNA Function in Tauopathies: A Case Study of miR-132/212

Cited by 5 publications

References 90 publications

Candidate Alzheimer’s Disease Biomarker miR-483-5p Lowers TAU Phosphorylation by Direct ERK1/2 Repression

Candidate Alzheimer’s Disease Biomarker miR-483-5p Lowers TAU Phosphorylation by Direct ERK1/2 Repression

A critical appraisal of tau‐targeting therapies for primary and secondary tauopathies

Targeting epigenetics: A novel promise for Alzheimer’s disease treatment

Contact Info

Product

Resources

About