Neurotrophin signaling is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Neurotrophins are a family of growth factors that play crucial roles in the development, survival, and function of neurons throughout the lifespan[1]. They include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4)[2]. Dysregulation of neurotrophin signaling has been strongly implicated in the pathogenesis of Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders[3].
Neurotrophins exert their effects by binding to two classes of receptors[4]:
The balance between pro-neurotrophins and mature neurotrophins, along with receptor expression patterns, determines the ultimate biological outcome.
NGF was the first discovered neurotrophic factor and is essential for[5]:
BDNF is the most widely expressed neurotrophin in the brain and is critical for[6]:
NT-3 supports[7]:
NT-4 is important for[8]:
Upon neurotrophin binding, Trk receptors dimerize and autophosphorylate, activating multiple downstream pathways[9]:
The p75^NTR receptor can activate diverse signaling pathways[10]:
NGF signaling is crucial for basal forebrain cholinergic neurons (BFCs), which are selectively vulnerable in AD[11]:
BDNF plays a critical role in synaptic plasticity mechanisms implicated in AD[12]:
Neurotrophin signaling intersects with tau pathology[13]:
BDNF supports dopaminergic neuron survival in the substantia nigra[14]:
Neurotrophin signaling may influence alpha-synuclein pathology:
Current trials are investigating:
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Ferrari E, Fiorenza D, Gradogna A, et al. Crosstalk between p75(NTR) and tau pathology in Alzheimer's disease. Brain Res Bull. 2020. ↩︎
Hyman C, Hofer M, Barde YA, et al. BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature. 1991. ↩︎