Screening and characterization of potential small molecule antagonists of myostatin.

Sarcopenia is the progressive loss of skeletal muscle mass and strength associated with aging. Current treatment of sarcopenia with hormone replacement therapy has been shown to have significant health risks, while exercise therapy is useful but cannot be prescribed in all cases of sarcopenia, often...

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Bibliographic Details
Main Author: Lee, Rachel Hui Min.
Other Authors: Susana Geifman Shochat
Format: Final Year Project
Language:English
Published: 2012
Subjects:
Online Access:http://hdl.handle.net/10356/49350
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Institution: Nanyang Technological University
Language: English
Description
Summary:Sarcopenia is the progressive loss of skeletal muscle mass and strength associated with aging. Current treatment of sarcopenia with hormone replacement therapy has been shown to have significant health risks, while exercise therapy is useful but cannot be prescribed in all cases of sarcopenia, often because the elderly suffer from pre-existing health conditions and drug treatments which preclude vigorous activity. Hence there is a need for new pharmacological treatments for sarcopenia. Myostatin, previously known as GDF-8, is a potent negative regulator of myoblast and satellite cell proliferation and differentiation. Small molecule inhibitors of myostatin, which can potentially antagonize the effects of myostatin, and thus encourage skeletal muscle regeneration, will be screened in this project to try to identify lead compounds which can be further developed into drugs treatments for sarcopenia in the elderly. In this project, screening of the 40 potential compounds with SPR biosensor technology and myoblast proliferation assays were used to identify two lead molecules to be tested further in animal trials.