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Neurotrophic factors in Alzheimer's disease: role of axonal transport.

Schindowski K, Belarbi K, Buée L - Genes Brain Behav. (2008)

Bottom Line: Furthermore, they are also associated with imbalanced distribution and dysregulation of NTF.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-beta (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.

View Article: PubMed Central - PubMed

Affiliation: Institut National de la Santé et de la Research Médicale U837, Université Lille 2, Lille Cedex, France. katharina.schindowski@lille.inserm.fr

ABSTRACT
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-beta (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.

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The neurotrophins and their receptors.
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fig01: The neurotrophins and their receptors.

Mentions: The most prominent members of the mammalian neurotrophin family are nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5). They activate various cell signaling pathways by activating two types of membrane-bound receptors, Trk (actually ‘tropomyosin-related kinase’ but recently ‘tyrosine receptor kinase’ is also used: TrkA, TrkB and TrkC) and p75NTR. These neurotrophins are synthesized as proneurotrophins that all bind to the p75NTR. In their active cleaved form, each neurotrophin selectively activates one of three types of Trk receptors (Fig. 1), NGF activates TrkA, NT-3 activates TrkC, while both BDNF and NT-4 activate TrkB receptors (Patapoutian & Reichardt 2001). The role of proneurotrophins and neurotrophins appears to be contradictory: while neurotrophins maintain survival and function, to certain neuronal populations, proneurotrophins trigger cell death through p75NTR (Friedman 2000).


Neurotrophic factors in Alzheimer's disease: role of axonal transport.

Schindowski K, Belarbi K, Buée L - Genes Brain Behav. (2008)

The neurotrophins and their receptors.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2228393&req=5

fig01: The neurotrophins and their receptors.
Mentions: The most prominent members of the mammalian neurotrophin family are nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5). They activate various cell signaling pathways by activating two types of membrane-bound receptors, Trk (actually ‘tropomyosin-related kinase’ but recently ‘tyrosine receptor kinase’ is also used: TrkA, TrkB and TrkC) and p75NTR. These neurotrophins are synthesized as proneurotrophins that all bind to the p75NTR. In their active cleaved form, each neurotrophin selectively activates one of three types of Trk receptors (Fig. 1), NGF activates TrkA, NT-3 activates TrkC, while both BDNF and NT-4 activate TrkB receptors (Patapoutian & Reichardt 2001). The role of proneurotrophins and neurotrophins appears to be contradictory: while neurotrophins maintain survival and function, to certain neuronal populations, proneurotrophins trigger cell death through p75NTR (Friedman 2000).

Bottom Line: Furthermore, they are also associated with imbalanced distribution and dysregulation of NTF.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-beta (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.

View Article: PubMed Central - PubMed

Affiliation: Institut National de la Santé et de la Research Médicale U837, Université Lille 2, Lille Cedex, France. katharina.schindowski@lille.inserm.fr

ABSTRACT
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-beta (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.

Show MeSH
Related in: MedlinePlus