Administrative Supplement: Connexin Function and Mechanisms of Cx26 Deficiency Induced Hearing Loss

  • Zhao, Hong-Bo (PI)

Grants and Contracts Details


Supplement of Alzheimer’s disease for R01DC019687-01 Abstract (the relevance to AD) Alzheimer''s disease (AD) is a neurodegenerative disease with a progressive loss of memory and cognitive decline. Hearing is an important neural-sensory input for cognition. Previous studies demonstrated that hearing loss could accelerate AD and dementia generation (Shahmiri et al., 2017; Swords et al., 2018; Thomson et al., 2017; Tuwaig et al., 2017; Haggstrom et al., 2018; Ford et al., 2018; Shen et al., 2018; Rochoy et al. 2019; Mansour et al., 2019; Murphy, 2019). It is well-known that gap junctional deficiency can induce hearing loss; Gap junction gene connexin mutations are responsible for more than 50% of nonsyndromic hearing loss. Our primary goal in the parent R01 is to investigate connexin gene hearing function and mechanisms underlying connexin mutation induced hearing loss. However, our preliminary studies also demonstrated that connexin gap junction deficiency can also accelerate and exacerbate age-related hearing loss (Zhao et al., 2019a&b). Since age-related hearing loss is a high-risk factor for AD dementia (Loughrey et al., 2018), we propose that connexin gap junctions may also have a role in AD generation and dementia development. Cx26 and Cx30 are predominant isoforms in the auditory system. Their mutations can cause hearing loss. In this supplement, we will examine whether deficiency of Cx26 and Cx30 can accelerate/exacerbate AD generation and development. Hearing loss, as an early AD biomarker (Liu et al., 2020), could be observed 5-10 years prior to an official AD diagnoses (Iliadou et al., 2003; Bateman et al., 2012; Haggstrom et al., 2018; Mansour et al., 2019). The proposed studies are urgently required and may provide important information for preventing or delaying AD generation and development. These studies will also real the role of connexin gap junctions in AD and may also shed light on the underlying mechanisms for AD generation.
Effective start/end date7/19/219/15/22


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