D-serine and its signaling pathway may represent a new druggable target for treating tinnitus

From a paper titled, “Physiopathological Relevance of D-Serine in the Mammalian Cochlea”, published on December 17, 2021:

Taken together, these results demonstrate for the first time that the neuro-messenger D-serine has a pivotal role in the cochlea by promoting the activation of silent cochlear NMDAR in pathological situations. Thus, D-serine and its signaling pathway may represent a new druggable target for treating sensorineural hearing disorders (i.e., hearing loss, tinnitus).

Aberrant NMDAR activation and related auditory nerve excitation are suspected factors of cochlear tinnitus induced by salicylate or noise exposures (Guitton et al., 2004; Van De Heyning et al., 2014; Bing et al., 2015). Accordingly, NMDAR inhibition is a promising pharmacological approach for the treatment of synaptopathic tinnitus (Bing et al., 2015). Here, we discover that D-serine is a necessary component of full NMDAR activation in the cochlea.

NMDAR inhibitors are not entirely new or unexplored (AM-101 for tinnitus is one good example). However, as this paper points out, these results (and a greater understanding of the role of D-serine) “may have important clinical implications by offering new opportunities in the modulation of NMDARs” — including new drug targets for chronic tinnitus.

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