Down-expression of P2RX2, KCNQ5, ERBB3 and SOCS3 through DNA hypermethylation in elderly women with presbycusis

Bouzid, Amal; Smeti, Ibtihel; Dhouib, Leila; Roche, Magali; Achour, I.; Khalfallah, Aida; Gibriel, Abdullah Ahmed; Charfeddine, Ilhem; Ayadi, Hammadi; Lachuer, Joël; Ghorbel, Abdelmonem; Petit, Christine; Masmoudi, Saber

doi:10.1080/1354750x.2018.1427795

Cited by 33 publications

(25 citation statements)

References 50 publications

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“…In addition, reduced expression of P2RX2, KCNQ5, ERBB3, and SOCS3 genes through DNA hypermethylation in elderly women was associated with presbycusis [48]. More recently, Bouzid et al demonstrated that hypermethylation of CpG site in the cadherin-23 (CDH23) gene is likely to be associated with presbycusis in elderly women [48]. These results implicate complex pathogenic mechanisms underlying ARHL.…”

Section: Dna Methylationmentioning

confidence: 95%

“…Furthermore, Xu et al [47] reported that hypermethylation of hearing-loss genes such as solute carrier family 26 member 4 (SLC26A4, DFNB4) and purinergic receptor P2X 2 (P2RX2, DFNA41) resulted in an increased risk for presbycusis in men. In addition, reduced expression of P2RX2, KCNQ5, ERBB3, and SOCS3 genes through DNA hypermethylation in elderly women was associated with presbycusis [48]. More recently, Bouzid et al demonstrated that hypermethylation of CpG site in the cadherin-23 (CDH23) gene is likely to be associated with presbycusis in elderly women [48].…”

Section: Dna Methylationmentioning

confidence: 99%

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Presbycusis: An Update on Cochlear Mechanisms and Therapies

Wang

Puel

2020

JCM

156

125

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Age-related hearing impairment (ARHI), also referred to as presbycusis, is the most common sensory impairment seen in the elderly. As our cochlea, the peripheral organ of hearing, ages, we tend to experience a decline in hearing and are at greater risk of cochlear sensory-neural cell degeneration and exacerbated age-related hearing impairments, e.g., gradual hearing loss, deterioration in speech comprehension (especially in noisy environments), difficulty in the localization sound sources, and ringing sensations in the ears. However, the aging process does not affect people uniformly; nor, in fact, does the aging process appear to be uniform even within an individual. Here, we outline recent research into chronological cochlear age in healthy people, and exacerbated hearing impairments during aging due to both extrinsic factors including noise and ototoxic medication, and intrinsic factors such as genetic predisposition, epigenetic factors, and aging. We review our current understanding of molecular pathways mediating ARHL and discuss recent discoveries in experimental hearing restoration and future prospects.

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Section: Dna Methylationmentioning

confidence: 95%

Section: Dna Methylationmentioning

confidence: 99%

Presbycusis: An Update on Cochlear Mechanisms and Therapies

Wang

Puel

2020

JCM

156

125

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“…Rare gain-or loss-of-function KCNQ5 gene variants (32) and KCNQ5 haploinsufficiency (33) cause severe intellectual disability and epileptic encephalopathy. KCNQ5 polymorphisms have also been associated with myopia (34), while KCNQ5 down-regulation is found in presbycusis (age-related hearing loss) (35). For most or all of these conditions, a KCNQ5-selective opener would be anticipated to have potential therapeutic activity.…”

Section: Significancementioning

confidence: 99%

KCNQ5 activation is a unifying molecular mechanism shared by genetically and culturally diverse botanical hypotensive folk medicines

Manville

Horst

Redford

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Botanical folk medicines have been used throughout human history to treat common disorders such as hypertension, often with unknown underlying mechanisms. Here, we discovered that hypotensive folk medicines from a genetically diverse range of plant species each selectively activated the vascular-expressed KCNQ5 potassium channel, a feature lacking in the modern synthetic pharmacopeia, whereas nonhypotensive plant extracts did not. Analyzing constituents of the hypotensive Sophora flavescens root, we found that the quinolizidine alkaloid aloperine is a KCNQ-dependent vasorelaxant that potently and isoform-selectively activates KCNQ5 by binding near the foot of the channel voltage sensor. Our findings reveal that KCNQ5-selective activation is a defining molecular mechanistic signature of genetically diverse traditional botanical hypotensives, transcending plant genus and human cultural boundaries. Discovery of botanical KCNQ5-selective potassium channel openers may enable future targeted therapies for diseases including hypertension and KCNQ5 loss-of-function encephalopathy.

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“…Alterations in both human and mouse methylation patterns have been hypothesized to play a role in the development of ARHL. In humans, hypermethylation and consequent decreased expression of several genes, including P2RX2 , KCNQ5 , ERBB3 , and SOCS3 , were observed in elderly women with ARHL (Bouzid, Smeti, Roche et al, ). Additionally, hypermethylation of SLC26A4 and P2RX2 conferred increased risk of ARHL in men (Xu et al, ).…”

Section: Epigeneticsmentioning

confidence: 99%

“…In elderly women with ARHL, the degree of CDH23 CpG site methylation in peripheral blood samples demonstrated a positive correlation with ARHL. These findings create the opportunity to employ methylation patterns readily obtained from blood samples as biomarkers for ARHL (Bouzid, Smeti, Roche et al, ).…”

Section: Epigeneticsmentioning

confidence: 99%

Advances in understanding of presbycusis

Tawfik

Klepper

Saliba

et al. 2019

J of Neuroscience Research

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The pathophysiology of age‐related hearing loss (ARHL), or presbycusis, involves a complex interplay between environmental and genetic factors. The fundamental biomolecular mechanisms of ARHL have been well described, including the roles of membrane transport, reactive oxygen species, cochlear synaptopathy, vascular insults, hormones, and microRNA, to name a few. The genetic basis underlying these mechanisms remains under‐investigated and poorly understood. The emergence of genome‐wide association studies has allowed for the identification of specific groups of genes involved in ARHL. This review highlights recent advances in understanding of the pathogenesis of ARHL, the genetic basis underlying these processes and suggests future directions for research and potential therapeutic avenues.

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Down-expression of P2RX2, KCNQ5, ERBB3 and SOCS3 through DNA hypermethylation in elderly women with presbycusis

Abstract: Down-expressed genes associated with DNA hypermethylation could be used as biomarkers for understanding complex pathogenic mechanisms underlying presbycusis.

Cited by 33 publications

References 50 publications

Presbycusis: An Update on Cochlear Mechanisms and Therapies

Presbycusis: An Update on Cochlear Mechanisms and Therapies

KCNQ5 activation is a unifying molecular mechanism shared by genetically and culturally diverse botanical hypotensive folk medicines

Advances in understanding of presbycusis

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