Modulating Nudix homology domain (NHD) with nicotinamide mononucleotide analogs and derivatives of same
AssigneesPresident and Fellows of Harvard College, Metro International Biotech, LLC
InventorsDavid A. Sinclair, Jun Li, Karl D. Normington
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Abstract
The invention provides methods of modulating and regulating NHD protein-protein interactions through nicotinamide mononucleotide, analogs and derivatives thereof, such as NAD+. Such modulation may be useful in methods of treating and preventing cancer, aging, cell death, radiation damage, radiation exposure, among others, may improve DNA repair, cell proliferation, cell survival, among others, and may increase the life span of a cell or protect it against certain stresses, among others.
Claims15
A method for recovering from, treating, or preventing cancer in a subject in need thereof comprising
- i) assessing protein-protein complexes in a sample from said subject, wherein said protein-protein complexes are between a first protein containing a Nudix Homology Domain (NHD) and a second protein which is different from the first protein and interacts with the NHD;
- ii) administering to the subject an effective amount of
- a) nicotinamide mononucleotide (NMN), or an analog or derivative thereof;
- or
- b) an agent that is not NMN or an analog or derivative thereof, wherein the agent increases the level of nicotinamide mononucleotide, or an analog or derivative thereof;
- or
- c) both a) and b);
- or
- d) an NHD-modulating agent that is not a) or b), wherein said NHD-modulating agent modulates protein-protein complex forming activity of the Nudix Homology Domain of said first protein in step (i).
A method for recovering from, treating, or preventing aging or cell death in a subject in need thereof comprising
- i) assessing protein-protein complexes in a sample from said subject, wherein said protein-protein complexes are between a first protein containing a Nudix Homology Domain (NHD) and a second protein which is different from the first protein and interacts with the NHD;
- ii) administering to the subject an effective amount of
- a) nicotinamide mononucleotide (NMN), or an analog or derivative thereof;
- or
- b) an agent that is not NMN or an analog or derivative thereof, wherein the agent increases the level of nicotinamide mononucleotide, or an analog or derivative thereof;
- or
- c) both a) and b);
- or
- d) an NHD-modulating agent that is not a) or b), wherein said NHD-modulating agent modulates protein-protein complex forming activity of the Nudix Homology Domain of said first protein in step (i).
A method for recovering from, treating, or preventing radiation damage or radiation exposure, recovering from, treating, or preventing chemotherapy-induced damage or cellular senescence, modulating DNA repair, or modulating cell proliferation or cell survival in a subject in need thereof comprising
- i) assessing protein-protein complexes in a sample from said subject, wherein said protein-protein complexes are between a first protein containing a Nudix Homology Domain (NHD) and a second protein which is different from the first protein and interacts with the NHD;
- ii) administering to the subject an effective amount of
- a) nicotinamide mononucleotide (NMN), or an analog or derivative thereof;
- or
- b) an agent that is not NMN or an analog or derivative thereof, wherein the agent increases the level of nicotinamide mononucleotide, or an analog or derivative thereof;
- or
- c) both a) and b);
- or
- d) an NHD-modulating agent that is not a) or b), wherein said NHD-modulating agent modulates protein-protein complex forming activity of the Nudix Homology Domain of said first protein in step (i).
Dependencies are inferred from the claim text.