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Published on: September 7, 2010
Signalling through the neurotrophin receptor p75NTR
1Max-Planck Institute for Psychiatry, Department of Neurobiochemistry Am Klopferspitz 18A, 82152 Martinsried, Germany. georg@neuro.mpg.de
Current Opinion in Neurobiology
|June 1, 1997
Summary
Nerve growth factor (NGF) promotes neuronal survival via TrkA receptors but can induce neuronal death through the p75 neurotrophin receptor (p75NTR). This dual role highlights NGF
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Signaling
Background:
- Neurotrophins, particularly nerve growth factor (NGF), are known for promoting neuronal survival through tyrosine kinase receptors.
- Recent research indicates NGF also engages the p75 neurotrophin receptor (p75NTR), a member of the tumor necrosis factor receptor family.
- p75NTR lacks intrinsic catalytic activity but binds all neurotrophins with nanomolar affinity.
Purpose of the Study:
- To elucidate the distinct signaling pathways activated by NGF through its receptors.
- To investigate the role of p75NTR in mediating NGF's effects on neuronal survival and death.
- To understand the differential activation of TrkA and p75NTR by NGF.
Main Methods:
- Analysis of neurotrophin receptor activation.
- Investigation of signaling pathways downstream of TrkA and p75NTR.
- Studies on neuronal survival and programmed cell death in response to NGF.
Main Results:
- NGF activates TrkA receptors, leading to neuronal survival.
- NGF uniquely activates p75NTR, a non-catalytic receptor, in trkA-negative neurons.
- Activation of p75NTR by NGF promotes programmed cell death during development.
Conclusions:
- NGF exhibits a dual role in neuronal fate determination, promoting survival via TrkA and death via p75NTR.
- The p75NTR pathway activated by NGF is crucial for eliminating trkA-negative neurons during development.
- Understanding these distinct signaling mechanisms is vital for neurobiology and therapeutic interventions.
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