Modulation of soluble Adenylyl Cyclase (sAC) as a Method of Altering Melanocyte Pigmentation
- Detailed Technology Description
- Pharmacologic soluble Adenylyl Cyclase (sAC) regulators have been identified as a new class in pigment modifying agents.
- Others
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Publications
Poster abstract: Increased melanogenesis ofhair and skin following topical soluble adenylyl cyclase inhibition
- *Abstract
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TechnologyOverview
Understanding how baseline pigmentation is controlled has numerousimplications due to its significance from both a psychological andhealth-related stand point. To date knowledge regarding signaling pathways thatcontrol pigmentation have been limited to changes in gene expression .
Melanin pigments are synthesized bymelanocytes in specialized organelles called melanosomes. Melanin is classifiedinto eumelanin and pheomelanin, which are made in eumelanosomes andpheomelanosomes, respectively.
While several key characteristics ofthe melanin pigment system such as identifying the enzymes needed for melaninsynthesis have been well studied, several other questions remain unanswered,such as what controls the activity of these enzymes after melanosomes areformed?
Cyclic AMP (cAMP) is a key signalingmolecule in the synthesis of melanin, and transmembrane adenylyl cyclases(tmACs) play a key role in melanogenesis. Melanosomal pH has been implicated inthe formation and maturation of melanosomes and in maintaining the ratio ofeumelanin to pheomelanin. However, the regulation of melanosomal pH by cAMP wasunknown.
The inventor has found that sAC, anon-canonical source of cAMP, acts as a pH sensor. The loss of sAC activity orthe use of sAC inhibitors, leads to elevated melanosomal pH levels, which inturn, leads to an increase in the synthesis of melanin. Thus, agents that canmodulate the levels of sAC could be used to regulate melanin pigment levels.
Further exploration of sAC’s role inmelanogenesis may offer new mechanisms that control human skin pigmentation andskin cancer risk, and due to the similarity between melanosomes, lysosomes andother organelles, understanding how sAC regulates organelle pH has implicationsfor other cells and tissues.
Topical treatment of mice with sACinhibitors has been shown to increase pigmentation in the skin and hair. Theseresults firmly establish a second cAMP-signaling pathway regulatingpigmentation, in which the loss of sAC-specific cAMP increases melaninproduction.
Neuromelanin is a dark pigment foundin the brain which is structurally related to melanin and is produced usingsimilar mechanisms as the skin. Patients with Parkinson's disease have beenshown to have 50% the amount of neuromelanin in the substantia nigra part ofthe brain as compared to similar patients of their same age, but withoutParkinson's. The death of neuromelanin-containing neurons in the brain havebeen linked to Parkinson's disease and also have been visualized in vivo withneuromelanin MRI. As it is believed that neuromlanin plays a vital role inpreventing cell death in certain parts of the brain, the ability to increaselevels of neuromelanin could be utilized for the treatment for Parkinson’sdisease.
Potential Applications
· Cosmetic applications for the darkening of skin or hair,such as self-tanning lotions or hair coloring using sAC inhibitors appliedtopically.
· Cancer prevention by raising eumelanin and decreasingpheomelanin
· Treatment of diseases of pigmentation such as albinism
· Modulation of neuromelanin as a treatment for Parkinson’sdisease.
- *Licensing
- Brian J. Kelly, Directorbjk44@cornell.edu646-962-7041
- Country/Region
- USA
