MicroRNAs and Presbycusis

Hu, Weiming; Wu, Junwu; Jiang, Wenjing; Tang, Jianguo

doi:10.14336/ad.2017.0119

Cited by 14 publications

(9 citation statements)

References 74 publications

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“…In the ear, microRNAs and their targets have been at the heart of many studies and excellent reviews for more than a decade (Wienholds et al, 2005 ; Weston et al, 2006 , 2011 ; Pierce et al, 2008 ; Soukup et al, 2009 ; Patel and Hu, 2012 ; Li et al, 2016a ; Riccardi et al, 2016 ; Wang Y. et al, 2016 ; Ebeid et al, 2017 ; Huang et al, 2017 ; Hu et al, 2018 ). In this time more than 400 miRNAs have been identified through traditional microarray studies (Weston et al, 2006 ; Wang et al, 2010 ; Elkan-Miller et al, 2011 ; Hertzano et al, 2011 ; Steijger et al, 2013 ; Zhang et al, 2013 , 2014 ) and RNA-Sequencing (Rudnicki et al, 2014 ; Riccardi et al, 2016 ), but only a handful has been characterized.…”

Section: Mrna Regulationmentioning

confidence: 99%

Intracellular Regulome Variability Along the Organ of Corti: Evidence, Approaches, Challenges, and Perspective

et al. 2018

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The mammalian hearing organ is a regular array of two types of hair cells (HCs) surrounded by six types of supporting cells. Along the tonotopic axis, this conserved radial array of cell types shows longitudinal variations to enhance the tuning properties of basilar membrane. We present the current evidence supporting the hypothesis that quantitative local variations in gene expression profiles are responsible for local cell responses to global gene manipulations. With the advent of next generation sequencing and the unprecedented array of technologies offering high throughput analyses at the single cell level, transcriptomics will become a common tool to enhance our understanding of the inner ear. We provide an overview of the approaches and landmark studies undertaken to date to analyze single cell variations in the organ of Corti and discuss the current limitations. We next provide an overview of the complexity of known regulatory mechanisms in the inner ear. These mechanisms are tightly regulated temporally and spatially at the transcription, RNA-splicing, mRNA-regulation, and translation levels. Understanding the intricacies of regulatory mechanisms at play in the inner ear will require the use of complementary approaches, and most probably, a combinatorial strategy coupling transcriptomics, proteomics, and epigenomics technologies. We highlight how these data, in conjunction with recent insights into molecular cell transformation, can advance attempts to restore lost hair cells.

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Section: Mrna Regulationmentioning

confidence: 99%

Intracellular Regulome Variability Along the Organ of Corti: Evidence, Approaches, Challenges, and Perspective

et al. 2018

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“…Particularly, because acoustic stimuli increase permeability of cation channels such as MET and TRP, the noise exposure also increases the AG uptake and directly accelerates intracellular accumulation of AGs within hair cells (Hayashida et al 1985;Park et al 2018;Ricci et al 2005). Age-related hearing loss, or presbycusis, caused by the degeneration of cochlear cells is also a major cause of preexisting hearing loss (Hu et al 2018). As tissue ages, the hair cells also undergo progressive oxidative mitochondrial DNA damage modified by excessive ROS generation and chronic inflammatory damage due to immunosenescence (Cui et al 2012;Iwai et al 2008;Kalinec et al 2017;Lee 2013;Saitoh et al 1994).…”

Section: Key Event 1: Prerequisite Events That Directly Impact Miementioning

confidence: 99%

Adverse outcome pathway for aminoglycoside ototoxicity in drug-resistant tuberculosis treatment

et al. 2019

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Individuals treated for multidrug-resistant tuberculosis (MDR-TB) with aminoglycosides (AGs) in resource-limited settings often experience permanent hearing loss. However, AG ototoxicity has never been conceptually integrated or causally linked to MDR-TB patients' pre-treatment health condition. We sought develop a framework that examines the relationships between pre-treatment conditions and AG-induced hearing loss among MDR-TB-infected individuals in sub-Saharan Africa.

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“…Mammalian vestibulocochlear hair cells are a stress-sensitive, nonregenerative cell type and, like the retinal cells of the eye, 1 are not replaced when they are injured or die. 10 , 13 , 14 , 29 , 57 , 60 , 82 , 84–86 Interestingly, emerging research indicates we selectively amplify directional sound in a noisy environment by unconsciously utilizing eye–ear coordination to integrate visual cues with the auditory information. 87 , 88 Assessing vision and oculomotor function is essential in the diagnostic evaluation of vestibulocochlear auditory impairments, 89 particularly in patients with idiopathic etiology.…”

Section: Mitochondrial Dysfunction In Hearing Lossmentioning

confidence: 99%

“… 24 , 39 In the more immediate future, shielding hair cells from oxidative damage and/or rescuing injured hair cells from falling into apoptosis by pharmacological treatment with free radical scavenging antioxidant compounds portend a promising therapeutic approach. 13 , 14 , 29 , 30 , 57 , 96–99 …”

Section: α-Lipoic Acid L -Carnitine and Butyratementioning

confidence: 99%

A New Approach to Treating Neurodegenerative Otologic Disorders

Moos

Faller

Glavas

et al. 2018

BioResearch Open Access

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Hearing loss, the most common neurological disorder and the fourth leading cause of years lived with disability, can have profound effects on quality of life. The impact of this “invisible disability,” with significant consequences, economic and personal, is most substantial in low- and middle-income countries, where >80% of affected people live. Given the importance of hearing for communication, enjoyment, and safety, with up to 500 million affected globally at a cost of nearly $800 billion/year, research on new approaches toward prevention and treatment is attracting increased attention. The consequences of noise pollution are largely preventable, but irreversible hearing loss can result from aging, disease, or drug side effects. Once damage occurs, treatment relies on hearing aids and cochlear implants. Preventing, delaying, or reducing some degree of hearing loss may be possible by avoiding excessive noise and addressing major contributory factors such as cardiovascular risk. However, given the magnitude of the problem, these interventions alone are unlikely to be sufficient. Recent advances in understanding principal mechanisms that govern hearing function, together with new drug discovery paradigms designed to identify efficacious therapies, bode well for pharmaceutical intervention. This review surveys various causes of loss of auditory function and discusses potential neurological underpinnings, including mitochondrial dysfunction. Mitochondria mitigate cell protection, survival, and function and may succumb to cumulative degradation of energy production and performance; the end result is cell death. Energy-demanding neurons and vestibulocochlear hair cells are vulnerable to mitochondrial dysfunction, and hearing impairment and deafness are characteristic of neurodegenerative mitochondrial disease phenotypes. Beyond acting as cellular powerhouses, mitochondria regulate immune responses to infections, and studies of this phenomenon have aided in identifying nuclear factor kappa B and nuclear factor erythroid 2-related factor 2/antioxidant response element signaling as targets for discovery of otologic drugs, respectively, suppressing or upregulating these pathways. Treatment with free radical scavenging antioxidants is one therapeutic approach, with lipoic acid and corresponding carnitine esters exhibiting improved biodistribution and other features showing promise. These compounds are also histone deacetylase (HDAC) inhibitors, adding epigenetic modulation to the mechanistic milieu through which they act. These data suggest that new drugs targeting mitochondrial dysfunction and modulating epigenetic pathways via HDAC inhibition or other mechanisms hold great promise.

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MicroRNAs and Presbycusis

Cited by 14 publications

References 74 publications

Intracellular Regulome Variability Along the Organ of Corti: Evidence, Approaches, Challenges, and Perspective

Intracellular Regulome Variability Along the Organ of Corti: Evidence, Approaches, Challenges, and Perspective

Adverse outcome pathway for aminoglycoside ototoxicity in drug-resistant tuberculosis treatment

A New Approach to Treating Neurodegenerative Otologic Disorders

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