Open AccessNeurotrophic factors in Alzheimer’s disease: role of axonal transport
Author(s) -
Schindowski K.,
Belarbi K.,
Buée L.
Publication year - 2008
Publication title -
genes, brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.315
H-Index - 91
eISSN - 1601-183X
pISSN - 1601-1848
DOI - 10.1111/j.1601-183x.2007.00378.x
Subject(s) - neuroscience , neurotrophin , basal forebrain , trk receptor , tropomyosin receptor kinase b , neurotrophic factors , nerve growth factor , cholinergic neuron , axoplasmic transport , neurofibrillary tangle , neocortex , cholinergic , alzheimer's disease , biology , senile plaques , receptor , medicine , disease , biochemistry
Neurotrophic factors (NTF) are small, versatile proteins that maintain survival and function to specific neuronal populations. In general, the axonal transport of NTF is important as not all of them are synthesized at the site of its action. Nerve growth factor (NGF), for instance, is produced in the neocortex and the hippocampus and then retrogradely transported to the cholinergic neurons of the basal forebrain. Neurodegenerative dementias like Alzheimer’s disease (AD) are linked to deficits in axonal transport. Furthermore, they are also associated with imbalanced distribution and dysregulation of NTF. In particular, brain‐derived neurotrophic factor (BDNF) plays a crucial role in cognition, learning and memory formation by modulating synaptic plasticity and is, therefore, a critical molecule in dementia and neurodegenerative diseases. Here, we review the changes of NTF expression and distribution (NGF, BDNF, neurotrophin‐3, neurotrophin‐4/5 and fibroblast growth factor‐2) and their receptors [tropomyosin‐related kinase (Trk)A, TrkB, TrkC and p75 NTR ] in AD and AD models. In addition, we focus on the interaction with neuropathological hallmarks Tau/neurofibrillary tangle and amyloid‐β (Abeta)/amyloid plaque pathology and their influence on axonal transport processes in order to unify AD‐specific cholinergic degeneration and Tau and Abeta misfolding through NTF pathophysiology.