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BDNF

Tuesday 23 September 2003

Definition: Brain-derived neurotrophic factor (BDNF) is one of the neurotrophic factors (neurotrophins or NTs) found in the brain and the periphery. BDNF was the second neurotrophic factor to be characterized after nerve growth factor (NGF). (WK)

BDNF acts on certain neurons of the central nervous system and the peripheral nervous system that helps to support the survival of existing neurons and encourage the growth and differentiation of new neurons and synapses.

In the brain, it is active in the hippocampus, cortex, and basal forebrain—areas vital to learning, memory, and higher thinking. BDNF is produced in the cortex but is released in the striatum, where it promotes cell survival. Huntingtin controls the microtubule-assisted vesicle transport of the brain-derived neurotrophic factor (BDNF).

However, despite its name, BDNF is actually found in a range of tissue and cell types, not just in the brain. It is also expressed in the retina, the CNS, motor neurons, the kidneys, and the prostate.

Action

BDNF binds at least two receptors on the surface of cells: NTRK2 (TrkB) (MIM.600456) and NGFR (or LNGFR for "low affinity nerve growth factor receptor", or p75 or TNFRSF16) (MIM.162010).

NTRK2 (TrkB) is a receptor tyrosine kinase (RTKs), as other related Trk receptors (NTRKs), as NTRK1 (TrkA) and NTRK3 (TrkC).

NGFR (LNGFR) plays a less clear role. NGFR binds and serves as a "sink" for neurotrophins. Cells which express both the LNGFR and the NTRKs receptors might therefore have a greater activity, since they have a higher "microconcentration" of the neurotrophin. It has also been shown, however, that the NGFR may signal a cell to die via apoptosis - so therefore cells expressing the NGFR in the absence of Trk receptors (NTRKs) may die rather than live in the presence of a neurotrophin.

Neurotrophins (NTs)

Neurotrophins, as BDNF or NTFs, are chemicals that help to stimulate and control neurogenesis, BDNF being one of the most active.

There are other neurotrophic factors structurally related to BDNF:

- NGF (Nerve Growth Factor) with two subunits NGFA (MIM.162030) and NGFB (MIM.162030)
- NTF3 (NT-3 for neurotrophin-3) (MIM.162660)
- NTF5 (NT-4 for neurotrophin-4 and NT-5 for neurotrophin-5) (MIM.162662)

While TrkB mediates the effects of BDNF and NT-4,TrkA binds and is activated by NGF, and TrkC binds and is activated by NT-3. NT-3 binds to TrkA and TrkB as well, but with less affinity.

Animal models

Mice born without the ability to make BDNF suffer developmental defects in the brain and sensory nervous system, and usually die soon after birth, suggesting that BDNF plays an important role in normal neural development.

Pathology

- germline mutations of BDNF in congenital central hypoventilation syndrome (MIM.209880) +/- Hirschsprung disease

- sequence variants associated