The expanding role of BDNF: a therapeutic target for Alzheimer's disease?

Abstract

Finding an effective treatment for chronic neurodegenerative disorders still represents an unmet goal. There is considerable evidence that such disorders represent a combination of genetic determinants and failure of neuroprotective mechanisms sparking a wider degree of interest in shedding light on the cellular changes responsible for these devastating disorders. Because of their role in survival or differentiation of developing neurons, as well as the recent discovery of their importance in regulating synaptic plasticity during adulthood, neurotrophic factors have been suggested as essential contributors of the etiology of neurodegenerative disorders. Alzheimer's disease (AD) is a complex, chronic, devastating disease that affects a high percentage of the population over 65 years of age. This review will focus on different pharmacological interventions that are currently in use or drugs under development, narrowing the therapeutic agents to those that interfere with the expression of the trophic factor brain-derived neurotrophic factor (BDNF), a molecule playing a pivotal role in synaptic plasticity and cognition. From these findings, it appears clear that BDNF is implicated in the mechanism of action of drugs that improve cognitive deficits in animal models of AD and in AD patients.

Targeting of neurotrophic factors, their receptors, and signaling pathways in the developmental neurotoxicity of organophosphates in vivo and in vitro

“…Given the vital role of NGF in neuronal differentiation into the cholinergic phenotype [5,19,36], adverse effects on ngfg expression may contribute to the particular sensitivity of these neurons to organophosphates [4,42,72,73]. Similarly, BDNF plays critical roles in neuronal cell differentiation, brain development and synaptic plasticity [51], and alterations in this trophic factor have been implicated in psychiatric diseases, neurodegenerative disorders and epilepsy [34,35,44,67,68,83].…”

Polygalasaponin XXXII from Polygala tenuifolia root improves hippocampal-dependent learning and memory

“…Increasing evidence indicates that BDNF plasma levels are significantly decreased in both elderly subjects and AD patients [17] ; this suggests that a decrease in BDNF levels could be associated with AD pathogenesis [31] . In the current study, expression of BDNF was reduced in the model group treated with scopolamine, which provided a potent evidence that scopolamine treatment could imitate the state of cognition in aging people or AD patients.…”

Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: Complexity of steroid hormone-growth factor interactions in the adult CNS

“…Although there are indications that this is not always true [131], and indeed there may be a redistribution rather than an absolute loss [21,22], this makes it unlikely that estrogen therapy would continue to be effective. As an alternate approach, rational drug design would suggest BDNF therapy, not only because of its potential to activate the signaling pathways normally attributed to estrogen, but it also would avoid the health risks associated with estrogen therapy [132]. And in contrast to estrogen, BDNF can increase its receptor, at least at low doses [133], potentially leading to enhanced efficacy.…”