Navitor Pharmaceuticals’ scientific founder makes landmark discovery of the molecular sensor for the amino acid leucine
Finding the long sought-after mediator of mTORC1 activation by leucine opens up opportunities for creating new medicines for metabolic, musculoskeletal, autoimmune and other age-related diseases.
Navitor Pharmaceuticals’ scientific founder, David M. Sabatini, has published ground-breaking research describing, for the first time, the identification and characterization of the cellular proteins responsible for sensing and mediating the metabolic effects of the amino acid leucine. The paper, published online in the journal Science, elucidates a key regulatory node related to leucine that was previously unknown within the multiple steps of the mTORC1 activation pathway.
The anabolic amino acid, leucine, is critical in cellular protein and lipid synthesis and directly regulates mammalian physiology including skeletal muscle growth, insulin secretion and food intake. As such, the ability to pharmacologically target the newly-discovered sensor for leucine opens a potential avenue for the modulation of mTORC1 to address healthspan and a range of diseases of aging including metabolic, neurodegenerative, autoimmune diseases, certain cancers, as well as age-related immune suppression and several genetic and rare diseases.
The discovery published in
“The discovery of this long sought-after mediator of mTORC1 activation by leucine opens up a novel and powerful approach to yield a new generation of drugs for multiple diseases of ageing. This is exactly aligned with Navitor’s approach to develop medicines that selectively target mTORC1 based on targeting critical cellular proteins involved in the activation of mTORC1 through nutrients such as amino acids and other components," said George P. Vlasuk, President and CEO of Navitor Pharmaceuticals.
“Leucine is one of the most physiologically important amino acids implicated in the regulation of mTORC1 activity; as such, it is a key driver of cellular growth and metabolism. This landmark discovery of the molecular sensor that links the availability of leucine to the activation status of mTORC1 in the cell facilitates a novel approach for the discovery and development of new drugs that can turn up or turn down mTORC1,” added Dr Vlasuk.
The mTORC1 molecular complex integrates multiple cellular signaling pathways in response to the availability of nutrients such as amino acids thereby serving as the primary central control point responsible for cellular growth and metabolism. The inhibition of mTORC1 has been demonstrated to address many diseases of ageing — including metabolic, neurodegenerative, autoimmune diseases, and certain cancers — as well as beneficially impacting healthspan leading to improved longevity in species as diverse as yeast to mice. In contrast, the reduced activity of mTORC1 is thought to play an important role in the atrophy of skeletal muscle associated with age (sarcopenia), immobilization and disease. Therefore, targeting cellular components involved in the regulation of mTORC1 activity that can yield both “inhibitors,” as well as “activators” of this complex offer a novel and powerful approach to the discovery and development of a new generation of drugs for the treatment of many diseases caused by the dysregulation of mTORC1.
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