Shedding light into the role of BDNF in the pharmacotherapy of Parkinson's disease

Abstract

Parkinson's disease (PD) is a chronic, neurodegenerative disease with a 1% incidence in the population over 55 years of age. Movement impairments represent undoubtedly the hallmark of the disorder; however, extensive evidence implicates cognitive deficits as concomitant peculiar features. Brainderived neurotrophic factor (BDNF) colocalizes with dopamine neurons in the substantia nigra, where dopaminergic cell bodies are located, and it has recently garnered attention as a molecule crucial for cognition, a function that is also compromised in PD patients. Thus, due to its colocalization with dopaminergic neurons and its role in cognition, BDNF might possess a dual role in PD, both as a neuroprotective molecule, since its inhibition leads to loss of nigral dopaminergic neurons, and as a neuromodulator, as its enhanced expression ameliorates cognitive processes. In this review, we discuss the mechanism of action of established as well as novel drugs for PD with a particular emphasis to those interfering with BDNF biosynthesis.

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].…”

Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory

“…Because of these properties, they have the potential to treat a variety of chronic and acute disorders of the CNS. Although there have been some successes, clinical use of classical neurotrophic factors, such as brain-derived neurotrophic factor, has been limited for technical reasons, including difficulty in crossing the blood-brain barrier (1,2). Therefore, the identification of small molecules that mimic some or all of the properties of neurotrophic factors could have significant potential for treating CNS disorders.…”

In vitro evaluation of cationic liposomal delivery of BDNF expressing plasmid DNA in experimental model of Parkinson's disease

“…On one side neurotrophin is essential for maintaining healthy neurons in the nigrostriatal circuitation, thus preventing movement deficits, while on the other hand; it actively participates in activity-dependent processes such as synaptic plasticity and cognition that are compromised in PD. [5] The mechanism by which it causes gene expression is depicted in the image below: Figure 3. BDNF-TrkB signalling pathway [6] BDNF binds TrkB with high affinity to induce its dimerization and also the autophosphorylation of tyrosine residues in the cytoplasmic kinase domain that serve as docking sites for effector molecules and trigger the activation of three main signalling pathways: PLCγ, PI3K and ERK cascades, which eventually causes phosphorylation and activation of the transcription factor CREB that mediates transcription of genes essential for the survival and differentiation of neurons.…”

“…reduced amount of the neurotrophin may be involved in the etiology and pathogenesis of PD. [5] Based on the BDNF deficit observed in PD patients at the nigrostriatal level, the likelihood to administer recombinant BDNF in order to preserve dopaminergic neurons and improve symptoms of the disease might well represent a therapeutic opportunity. [5] 3.6 The blood-brain barrier components of a neurovascular unit [7] The blood-brain barrier (BBB) is primarily composed of the brain endothelial cells.…”

“…[5] Based on the BDNF deficit observed in PD patients at the nigrostriatal level, the likelihood to administer recombinant BDNF in order to preserve dopaminergic neurons and improve symptoms of the disease might well represent a therapeutic opportunity. [5] 3.6 The blood-brain barrier components of a neurovascular unit [7] The blood-brain barrier (BBB) is primarily composed of the brain endothelial cells. Extracellular base membrane, adjacent pericytes, perivascular astrocytes, and microglia are the other structures, which constitute the neurovascular unit that is an integral part of the BBB.…”