Fast-Trk(B)ing the mechanism of antidepressants

Conroy, Jacinta; Jhaveri, Dhanisha J.; Coulson, Elizabeth J.

doi:10.1016/j.neuron.2021.04.027

Cited by 3 publications

(2 citation statements)

References 9 publications

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“…The revolutionary potential of this possible discovery and the key role MD has played in it cannot be understated and already have been widely commented upon in the neuroscience community [1009][1010][1011][1012]; attempts have already been made to find small molecules which directly activate TRKB [1013] or positively stimulate BDNF signaling [1014]. We finally come to the last category of membrane-associated proteins, and arguably the most difficult to study of all: peripheral membrane proteins.…”

Section: Tropomyosin Receptor Kinase Bmentioning

confidence: 99%

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

2021

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We review the use of molecular dynamics (MD) simulation as a drug design tool in the context of the role that the lipid membrane can play in drug action, i.e., the interaction between candidate drug molecules and lipid membranes. In the standard “lock and key” paradigm, only the interaction between the drug and a specific active site of a specific protein is considered; the environment in which the drug acts is, from a biophysical perspective, far more complex than this. The possible mechanisms though which a drug can be designed to tinker with physiological processes are significantly broader than merely fitting to a single active site of a single protein. In this paper, we focus on the role of the lipid membrane, arguably the most important element outside the proteins themselves, as a case study. We discuss work that has been carried out, using MD simulation, concerning the transfection of drugs through membranes that act as biological barriers in the path of the drugs, the behavior of drug molecules within membranes, how their collective behavior can affect the structure and properties of the membrane and, finally, the role lipid membranes, to which the vast majority of drug target proteins are associated, can play in mediating the interaction between drug and target protein. This review paper is the second in a two-part series covering MD simulation as a tool in pharmaceutical research; both are designed as pedagogical review papers aimed at both pharmaceutical scientists interested in exploring how the tool of MD simulation can be applied to their research and computational scientists interested in exploring the possibility of a pharmaceutical context for their research.

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Section: Tropomyosin Receptor Kinase Bmentioning

confidence: 99%

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

2021

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“…Interestingly, BDNF, acting on the ventral tegmental area (VTA)–nucleus accumbens (NAc) signaling pathway, can induce a depression-like phenotype [ 142 ]. Numerous recent studies indicated that BDNF and/or tropomyosin receptor kinase B (TrkB) signaling pathways could play important roles in the rapid antidepressant effects of ketamine [ 143 ]. For example, BDNF might trigger a mammalian target of the rapamycin protein (mTOR) signaling pathway, causing synaptogenesis [ 144 , 145 ].…”

Section: Relationship Between Inflammation and Depressionmentioning

confidence: 99%

α7 Nicotinic acetylcholine receptor: a key receptor in the cholinergic anti-inflammatory pathway exerting an antidepressant effect

Liu

Zhang

Shi

et al. 2023

J Neuroinflammation

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Depression is a common mental illness, which is related to monoamine neurotransmitters and the dysfunction of the cholinergic, immune, glutamatergic, and neuroendocrine systems. The hypothesis of monoamine neurotransmitters is one of the commonly recognized pathogenic mechanisms of depression; however, the drugs designed based on this hypothesis have not achieved good clinical results. A recent study demonstrated that depression and inflammation were strongly correlated, and the activation of alpha7 nicotinic acetylcholine receptor (α7 nAChR)-mediated cholinergic anti-inflammatory pathway (CAP) in the cholinergic system exhibited good therapeutic effects against depression. Therefore, anti-inflammation might be a potential direction for the treatment of depression. Moreover, it is also necessary to further reveal the key role of inflammation and α7 nAChR in the pathogenesis of depression. This review focused on the correlations between inflammation and depression as well-discussed the crucial role of α7 nAChR in the CAP.

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Aripiprazole attenuates the medial prefrontal cortex morphological and biochemical alterations in rats with neonatal ventral hippocampus lesion

Flores-Gómez

Apam-Castillejos

Juárez-Díaz

et al. 2023

Journal of Chemical Neuroanatomy

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Fast-Trk(B)ing the mechanism of antidepressants

Cited by 3 publications

References 9 publications

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

α7 Nicotinic acetylcholine receptor: a key receptor in the cholinergic anti-inflammatory pathway exerting an antidepressant effect

Aripiprazole attenuates the medial prefrontal cortex morphological and biochemical alterations in rats with neonatal ventral hippocampus lesion

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