neurotrophin

Pharmacological exploitation of neurotrophins and their receptors to develop novel therapeutic approaches against neurodegenerative diseases and brain trauma

Neurotrophins (NGF, BDNF, NT-3) are endogenous growth factors that exert neuroprotective effects by preventing neuronal death and promoting neurogenesis. They act by binding to their respective high-affinity, pro-survival receptors TrkA, TrkB or TrkC, as well as to p75NTR death receptor. While these molecules have been shown to significantly slow or prevent neurodegeneration, their reduced bioavailability and inability to penetrate the blood-brain-barrier limit their use as potential therapeutics. To bypass these limitations, our research team has developed and patented small-sized, lipophilic compounds which selectively resemble neurotrophins’ effects, presenting preferable pharmacological properties and promoting neuroprotection and repair against neurodegeneration. In addition, the combination of these molecules with 3D cultured human neuronal cells, and their targeted delivery in the brain ventricles through soft robotic systems, could offer novel therapeutic approaches against neurodegenerative diseases and brain trauma.

Neuronal plasticity and neurotrophin signaling as the common mechanism for antidepressant effect

Neuronal plasticity has for a long time been considered important for the recovery from depression and for the antidepressant drug action, but how the drug action is translated to plasticity has remained unclear. Brain-derived neurotrophic factor (BDNF) and its receptor TRKB are critical regulators of neuronal plasticity and have been implicated in the antidepressant action. We have recently found that many, if not all, different antidepressants, including serotonin selective SSRIs, tricyclic as well as fast-acting ketamine, directly bind to TRKB, thereby promoting TRKB translocation to synaptic membranes, which increases BDNF signaling. We have previously shown that antidepressant treatment induces a juvenile-like state of activity in the cortex that facilitates beneficial rewiring of abnormal networks. We recently showed that activation of TRKB receptors in parvalbumin-containing interneurons orchestrates cortical activation states and is both necessary and sufficient for the antidepressantinduced cortical plasticity. Our findings open a new framework how the action of antidepressants act: rather than regulating brain monoamine concentrations, antidepressants directly bind to TRKB and allosterically promote BDNF signaling, thereby inducing a state of plasticity that allows re-wiring of abnormal networks for better functionality.

Structural plasticity by neurotrophins and Tolls in Drosophila

Biological characterisation of new microneurotrophin mimetics in countering neurodegeneration

Deciphering the role of p75 neurotrophin receptor in adult neurogenesis: a potential pharmacological target against Alzheimer’s Disease

Defining the role of the p75 Neurotrophin Receptor in altering neuronal function, neuroinflammation and cognitive decline in Alzheimer’s disease

Neurotrophin-3/TrkC contribution to fear extinction and regulation of glutamatergic synapses

The role of prefrontal somatostatin interneurons and neurotrophin signaling in stress coping

The modulation of p75 neurotrophin receptor reduces oxidative stress and inflammation in a cellular model of Rett syndrome

FENS Forum 2024

Neurotrophins in adolescent brain rat are not altered by methamphetamine exposure during early postnatal period

FENS Forum 2024