A5068068737- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Nerve injury and regeneration
- Stress Responses and Cortisol
- Treatment of Major Depression
- Proteoglycans and glycosaminoglycans research
- Neuropeptides and Animal Physiology
- Tryptophan and brain disorders
- Renin-Angiotensin System Studies
- Neurotransmitter Receptor Influence on Behavior
- Pharmacological Receptor Mechanisms and Effects
- SARS-CoV-2 and COVID-19 Research
- Cellular transport and secretion
- Protein Tyrosine Phosphatases
- Protein Kinase Regulation and GTPase Signaling
- Chemical Reaction Mechanisms
- Gene Regulatory Network Analysis
- Photoreceptor and optogenetics research
- Drug-Induced Ocular Toxicity
- Cytokine Signaling Pathways and Interactions
- Calpain Protease Function and Regulation
- Advanced Control Systems Optimization
- Psychedelics and Drug Studies
- Schizophrenia research and treatment
- Retinal Development and Disorders
University of Helsinki
2017-2023
It is unclear how binding of antidepressant drugs to their targets gives rise the clinical effect. We discovered that transmembrane domain tyrosine kinase receptor 2 (TRKB), brain-derived neurotrophic factor (BDNF) promotes neuronal plasticity and responses, has a cholesterol-sensing function mediates synaptic effects cholesterol. then found both typical fast-acting antidepressants directly bind TRKB, thereby facilitating localization TRKB its activation by BDNF. Extensive computational...
Abstract Psychedelics produce fast and persistent antidepressant effects induce neuroplasticity resembling the of clinically approved antidepressants. We recently reported that pharmacologically diverse antidepressants, including fluoxetine ketamine, act by binding to TrkB, receptor for BDNF. Here we show lysergic acid diethylamide (LSD) psilocin directly bind TrkB with affinities 1,000-fold higher than those other psychedelics antidepressants distinct but partially overlapping sites within...
Repurposing of currently available drugs is a valuable strategy to tackle the consequences COVID-19. Recently, several studies have investigated effect psychoactive on SARS-CoV-2 in cell culture models as well clinical practice. Our aim was expand these and test some compounds against newly emerged variants. Several antidepressants antipsychotic with different primary mechanisms action were tested ACE2/TMPRSS2-expressing human embryonic kidney cells infection by spike protein-dependent...
Perineuronal nets (PNNs) are an extracellular matrix structure rich in chondroitin sulfate proteoglycans (CSPGs), which preferentially encase parvalbumin-containing (PV + ) interneurons. PNNs restrict cortical network plasticity but the molecular mechanisms involved unclear. We found that reactivation of ocular dominance adult visual cortex induced by chondroitinase ABC (chABC)-mediated PNN removal requires intact signaling neurotrophin receptor TRKB PV neurons. Additionally, we demonstrate...
Nitric oxide (NO) has been long recognized as an important modulator of neural plasticity, but characterization the molecular mechanisms involved - specially guanylyl cyclase-independent ones challenging. There is evidence that NO could modify BDNF-TRKB signaling, a key mediator neuronal plasticity. However, mechanism underlying interplay and TRKB remains unclear. Here we show induces nitration tyrosine 816 in receptor vivo vitro, post-translational modification inhibits phosphorylation...
The renin-angiotensin system (RAS) is associated with peripheral fluid homeostasis and cardiovascular function, but recent evidence also suggests a functional role in the brain. RAS regulates physiological behavioral parameters related to stress response, including depressive symptoms. Apparently, can modulate levels of brain-derived neurotrophic factor (BDNF) TRKB, which are important neurobiology depression antidepressant action. However, interaction between BDNF/TRKB has not been...
Ketamine, a well-known anesthetic, has recently attracted renewed attention as fast-acting antidepressant. A single dose of ketamine induces rapid synaptogenesis, which may underlie its antidepressant effect. To test whether repeated exposure to triggers sustained we administered sub-anesthetic (10 mg/kg i.p.) once-daily for 5 days, and repeatedly imaged dendritic spines the YFP-expressing pyramidal neurons in somatosensory cortex awake female mice using vivo two-photon microscopy. We found...
Cholesterol is an essential constituent of cell membranes. The discovery cholesterol-recognition amino acid consensus (CRAC) motif in proteins indicated a putative direct, non-covalent interaction between cholesterol and proteins. In the present study, we evaluated presence CRAC its inverted version (CARC) transmembrane region (TMR) tyrosine kinase receptor family (RTK) several species using silico methods. motifs were found across all analyzed, while CARC was only vertebrates....
Abstract Background and Purpose Repurposing of currently available drugs is a valuable strategy to tackle the consequences COVID-19. Recently, several studies have investigated effect psychoactive on SARS-CoV-2 in cell culture models as well clinical practice. Our aim was expand these test some compounds against newly emerged variants. Experimental Approach Several antidepressant antipsychotic with different primary mechanisms action were tested ACE2/TMPRSS2-expressing human embryonic kidney...
Perineuronal nets (PNNs) have an important physiological role in the retention of learning by restricting cognitive flexibility. Their deposition peaks after developmental periods intensive learning, usually late childhood, and they help long-term preservation newly acquired skills information. Modulation PNN function various techniques enhances plasticity regulates memories, which may be beneficial when memory persistence entails negative symptoms such as post-traumatic stress disorder...
Abstract Brain derived neurotrophic factor (BDNF) and its receptor tropomyosin kinase B (TRKB) are key regulators of activity‐dependent plasticity in the brain. TRKB is target for both slow‐ rapid‐acting antidepressants BDNF–TRKB system mediates plasticity‐inducing effects through their downstream targets. Particularly, protein complexes that regulate trafficking synapse recruitment receptors might be crucial this process. In present study, we investigated interaction with postsynaptic...
Abstract It is unclear how binding of antidepressant drugs to their targets gives rise the clinical effect. We discovered that transmembrane domain TRKB, brain-derived neurotrophic factor (BDNF) receptor promotes neuronal plasticity and responses, has a cholesterol-sensing function mediates synaptic effects cholesterol. then found both typical fast-acting antidepressants directly bind thereby facilitating localization TRKB its activation by BDNF. Extensive computational approaches including...
Abstract Cholesterol is an essential constituent of cell membranes. Recently, the discovery cholesterol recognition amino acid consensus (CRAC) on proteins indicated a putative direct, non-covalent interaction between and proteins. In present study, we evaluated presence CRAC motif its inverted version (CARC) in transmembrane region (TMR) tyrosine kinase receptor family (RTK) several species using silico methods. motifs were found across all analyzed, while CARC was only vertebrates. The...
Abstract Antidepressant drugs activate TRKB (tropomyosin-related kinase B), however it remains unclear whether these compounds employ a common mechanism for achieving this effect. We found by using mass spectrometry that the interaction of several proteins with was disrupted in hippocampus fluoxetine-treated animals (single intraperitoneal injection), including members AP-2 complex (adaptor protein complex-2) involved vesicular endocytosis. The cargo-docking mu subunit (AP2M) both acute and...
Abstract Perineuronal nets (PNNs) are an extracellular matrix structure rich in chondroitin sulphate proteoglycans (CSPGs) which preferentially encase parvalbumin-containing (PV+) interneurons. PNNs restrict cortical network plasticity but the molecular mechanisms involved unclear. We found that reactivation of ocular dominance adult visual cortex induced by chondroitinase (chABC)-mediated PNN removal requires intact signaling neurotrophin receptor TRKB PV+ neurons. Additionally, we...
ABSTRACT Renin-angiotensin system (RAS) is associated to peripheral fluid homeostasis and cardiovascular function, but recent evidence has also drawn its functional role in the brain. RAS been described regulate physiological behavioral parameters related stress response, including depressive symptoms. Apparently, can modulate levels of brain derived neurotrophic factor (BDNF) TRKB, which are important neurobiology depression antidepressant action. However, interaction between BDNF/TRKB...
Abstract Nitric oxide has been long recognized as an important modulator of neural plasticity, but characterization the molecular mechanisms involved - specially guanylyl cyclase-independent ones challenging. There is evidence that NO could modify BDNF-TRKB signaling, a key mediator neuronal plasticity. However, mechanism underlying interplay and TRKB remains unclear. Here we show nitric induces nitration tyrosine 816 in receptor vivo vitro, post-translational modification inhibits...