Front Aging Neurosci. 2015 Apr 23;7:60. doi: 10.3389/fnagi.2015.00060. eCollection 2015.
Sphingosine 1-phosphate signaling pathway in inner ear biology. New therapeutic strategies for hearing loss?
Abstract
Hearing
loss is one of the most prevalent conditions around the world, in
particular among people over 60 years old. Thus, an increase of this
affection is predicted as result of the aging process in our population.
In this context, it is important to further explore the function of
molecular targets involved in the biology of inner ear sensory cells to
better individuate new candidates for therapeutic application. One of
the main causes of deafness resides into the premature death of hair
cells and auditory neurons. In this regard, neurotrophins and growth
factors such as insulin
like growth factor are known to be beneficial by favoring the survival
of these cells. An elevated number of published data in the last 20
years have individuated sphingolipids not only as structural components
of biological membranes but also as critical regulators of key
biological processes, including cell survival. Ceramide,
formed by catabolism of sphingomyelin (SM) and other complex
sphingolipids, is a strong inducer of apoptotic pathway, whereas
sphingosine 1-phosphate (S1P), generated by cleavage of ceramide
to sphingosine and phosphorylation catalyzed by two distinct
sphingosine kinase (SK) enzymes, stimulates cell survival. Interestingly
S1P, by acting as intracellular mediator or as ligand of a family of
five distinct S1P receptors (S1P1-S1P5), is a very powerful bioactive
sphingolipid, capable of triggering also other diverse cellular
responses such as cell migration, proliferation and differentiation, and
is critically involved in the development and homeostasis of several
organs and tissues. Although new interesting data have become available,
the information on S1P pathway and other sphingolipids in the biology
of the inner ear is limited. Nonetheless, there are several lines of
evidence implicating these signaling molecules during neurogenesis in
other cell populations. In this review, we discuss the role of S1P
during inner ear development, also as guidance for future studies.
KEYWORDS:
auditory neurons; growth factors; hearing loss; inner ear neurogenesis; neurotrophins; sensory hair-cells; sphingolipids; sphingosine 1-phosphate- PMID:
- 25954197
- [PubMed]
- PMCID:
- PMC4407579
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