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Brain-derived neurotrophic factor (BDNF), or abrineurin, [5] is a protein [6] that, in humans, is encoded by the BDNF gene. [ 7 ] [ 8 ] BDNF is a member of the neurotrophin family of growth factors, which are related to the canonical nerve growth factor (NGF), a family which also includes NT-3 and NT-4 /NT-5.
ALTO-100, previously known as NSI-189 (NeuralStem Inc. 189), [3] is a drug described as a hippocampal neurogenesis stimulant and indirect brain-derived neurotrophic factor (BDNF) modulator which is under development for the treatment of major depressive disorder (MDD), bipolar depression, and post-traumatic stress disorder (PTSD).
BDNF is involved in depression through its effects on serotonin. BDNF has been shown to promote the development, function, and expression of serotonergic neurons. [28] Because more active serotonin results in more positive moods, antidepressants work to increase serotonin levels.
The benzothiazole riluzole exerts neuroprotective effects by increasing BDNF and GDNF levels with improvement of motor neuron survival. It has been approved for the treatment of ALS and delays the onset of ventilator-dependence or tracheostomy in some people and may increase survival by two to three months. [23]
Many antidepressant drugs acutely increase synaptic levels of the monoamine neurotransmitter, serotonin, but they may also enhance the levels of norepinephrine and dopamine. The observation of this efficacy led to the monoamine hypothesis of depression , which postulates that the deficit of certain neurotransmitters is responsible for ...
Serotonin levels within the synapse drop, then rise again, ultimately leading to downregulation of post-synaptic serotonin receptors. [183] Other, indirect effects may include increased norepinephrine output, increased neuronal cyclic AMP levels, and increased levels of regulatory factors such as BDNF and CREB. [184]
Studies have shown that corticosterone treatment and adrenalectomy reduces or upregulated hippocampal BDNF expression. [9] Consistent between human and animal studies, BDNF levels are decreased in those with untreated major depression. [9] However, the correlation between BDNF levels and depression is controversial. [9] [10]
However, they have been shown to cause DNA demethylation, possibly due to an increase in the levels of TET1, which is a demethylating enzyme. [84] In the human peripheral cells of patients with anxiety disorders and in animal models of anxiety disorders, genes such as GAD1 , NR3C1, BDNF, MAOA , HECA, and FKBP5 are shown to be hypermethylated.