Novel Roles of a DNA Repair Protein, DNA-PKcs, in Obesity, Neurological Function, and Aging

Description:
The catalytic subunit of the DNA-dependent protein kinase complex (DNA-PKcs) has been shown to be important in DNA repair and VDJ recombination in lymphocytes. The inventors have discovered that DNA-PKcs also plays novel, important roles in energy regulation and neurological function. The inventors observed that mature DNA-PKcs-deficient mice (also known as SCID mice) have a lower proportion of fat, resist obesity, and have significantly greater physical endurance than wild-type control mice, particularly with increasing age. The inventors also observed that DNA-PKcs-deficient mice have better memory and less anxiety. One potential explanation for this is that they express higher levels of brain-derived neurotrophic factor (BDNF), which is associated with neurogenesis, memory formation and suppression of anxiety and depression. Moreover, DNA-PKcs-deficient cells produce less oxidative stress. Thus, inhibition of DNA-PKcs may have unexpected utility in the treatment of a wide range of diseases and conditions.

The invention discloses methods of inhibiting DNA-PKcs activity to decrease adiposity, improve physical endurance and increase insulin sensitivity and the number of mitochondria. Also claimed are methods directed to improved neurological function, such as methods for protection from neurodegenerative disease, improving memory and learning ability, and for reducing depression and anxiety. Additionally, the invention discloses methods for reducing inflammation and for treating heart disease.
Patent Information:
For Information, Contact:
Pragnesh Mistry
Technology Transfer Manager
NIH Technology Transfer
301-435-4616
pragnesh.mistry@nih.gov
Inventors:
Jay Chung
Keywords:
Aging
ANXIETY
Cardiovascular
depression
DIABETES
DNA-Dependent
DNA-PKcs
Endurance
Energy
HEART
IB1XXX
IB3XXX
IB6XXX
IBXXXX
Inflammation
insulin
INSULIN-DEPENDENT
IXXXXX
LEARNING
MEMORY
METABOLIC
Metabolism
Mitochondria
Neurological
OBESITY
REGULATION
TYPE-2
Weight
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