Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:6.5.1.2 (
DNA ligase
)
2,749
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Brain-derived neurotrophic factor
(
BDNF
) promotes the survival and growth of neurons during brain development and mediates activity-dependent synaptic plasticity and associated learning and memory in the adult.
BDNF
levels are reduced in brain regions affected in Alzheimer's, Parkinson's, and Huntington's diseases, and elevation of
BDNF
levels can ameliorate neuronal dysfunction and degeneration in experimental models of these diseases. Because neurons accumulate oxidative lesions in their DNA during normal activity and in neurodegenerative disorders, we determined whether and how
BDNF
affects the ability of neurons to cope with oxidative DNA damage. We found that
BDNF
protects cerebral cortical neurons against oxidative DNA damage-induced death by a mechanism involving enhanced DNA repair.
BDNF
stimulates DNA repair by activating cyclic AMP response element-binding protein (CREB), which, in turn, induces the expression of apurinic/apyrimidinic endonuclease 1 (APE1), a key enzyme in the base excision DNA repair pathway. Suppression of either APE1 or TrkB by RNA interference abolishes the ability of
BDNF
to protect neurons against oxidized DNA damage-induced death. The ability of
BDNF
to activate CREB and upregulate APE1 expression is abolished by shRNA of TrkB as well as inhibitors of TrkB, PI3 kinase, and Akt kinase. Voluntary running wheel exercise significantly increases levels of
BDNF
, activates CREB, and upregulates APE1 in the cerebral cortex and hippocampus of mice, suggesting a novel mechanism whereby exercise may protect neurons from oxidative DNA damage. Our findings reveal a previously unknown ability of
BDNF
to enhance DNA repair by inducing the expression of the
DNA repair enzyme
APE1.
...
PMID:BDNF and exercise enhance neuronal DNA repair by stimulating CREB-mediated production of apurinic/apyrimidinic endonuclease 1. 2411 93
