Besides Huntington's disease, does brain-type creatine kinase play a role in other forms of hearing impairment resulting from a common pathological cause?

Abstract

Hearing impairment following cochlear damage due to noise trauma, ototoxicity caused by aminoglycoside antibiotics, or age-related cochlear degeneration was linked to a common pathogenesis involving the formation of reactive oxygen species (ROS). Cochleae are more vulnerable to oxidative stress than other organs because of the high metabolic demands of their mechanosensory hair cells in response to sound stimulation. We recently showed that patients and mice with Huntington's disease (HD) have hearing impairment and that the dysregulated phosphocreatine (PCr)-creatine kinase (CK) system may account for this auditory dysfunction. Given the importance of noninvasive biomarkers and the easy access of hearing tests, the symptom of hearing loss in HD patients may serve as a useful clinical indicator of disease onset and progression of HD. We also showed that dietary creatine supplementation rescued the impaired PCr-CK system and improved the expression of cochlear brain-type creatine kinase (CKB) in HD mice, thereby restoring their hearing. Because creatine is an antioxidant, we postulated that creatine might enhance expression of CKB by reducing oxidative stress. In addition to HD-related hearing impairment, inferior CKB expression and/or an impaired PCr-CK system may also play an important role in other hearing impairments caused by elevated levels of ROS. Most importantly, dietary supplements may be beneficial to patients with these hearing deficiencies.

Comparison of Genomic and Epigenomic Expression in Monozygotic Twins Discordant for Rett Syndrome

“…Furthermore, CKB is decreased in the brains of patients with neurodegenerative disorders including Alzheimer disease, Huntington disease, and Pick disease [54]–[56]. CKB also has an important role in the bone-reabsorption function of osteoclasts [57].…”

Cellular compartmentation of energy metabolism: creatine kinase microcompartments and recruitment of B-type creatine kinase to specific subcellular sites

“…This is also seen in the clinics with patients suffering from Cr deficiency syndromes or from pathologies known for their diminished BCK activity such as neurodegenerative Alzheimer and Huntington diseases (Lin et al 2013;Burklen et al 2006). Hearing loss in Huntington's disease may be directly related to dysfunctional Ca 2+ handling due to reduced BCK activity, resulting from either ROS-induced BCK damage or inhibition of BCK promoters by Huntingtin in the elderly (Lin et al 2011b;Lin et al 2013). BCK expression is highly regulated by various signals, including estrogens (Reiss and Kaye 1981), p53 (Zhao et al 1994), or interferon gamma (Kim et al 2012), and dysregulation is often seen in various pathologies, with cancer probably being the best studied (see the contribution by Yan 2016 in this issue).…”

An Oral Combination of Vitamins A, C, E, and Mg++ Improves Auditory Thresholds in Age-Related Hearing Loss

“…This, in turn, would induce oxidative damage and loss of hair cells, supporting cells, ganglion cells, and fibrocytes in the stria vascularis ( Bielefeld et al, 2010 ; Huang and Tang, 2010 ; Fetoni et al, 2011 ; Yamasoba et al, 2013 ; Fujimoto and Yamasoba, 2014 ; Alvarado et al, 2015b ; Melgar-Rojas et al, 2015b ). Excess free radical formation seems to be part of a common pathogenic pathway ( Alvarado et al, 2015b ; Tavanai and Mohammadkhani, 2017 ) which is involved in other forms of hearing loss such as NIHL and DIHL ( Henderson et al, 2006 ; Le Prell et al, 2007a , b ; Bielefeld et al, 2010 ; Fetoni et al, 2011 ) as weel as in many neurodegenerative pathologies ( Ames et al, 1993 ; Lin and Beal, 2006 ; Gardiner et al, 2009 ) that present high incidence of hearing loss ( Lin Y.S. et al, 2011 ; Vitale et al, 2012 ; Hung et al, 2015 ; Hardy et al, 2016 ; Folmer et al, 2017 ; Profant et al, 2017 ; Zheng et al, 2017 ).…”