更新于：2024-11-01

TrkB x TrkA x p75NTR x BDNF

更新于：2024-11-01

基本信息

关联

项与 TrkB x TrkA x p75NTR x BDNF 相关的药物

AC-25793

靶点

BDNF x TrkA x TrkB x p75NTR

作用机制

BDNF调节剂 [+3]

在研机构

AlzeCure Pharma AB [+1]

原研机构

AlzeCure Pharma AB

在研适应症

阿尔茨海默症

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 TrkB x TrkA x p75NTR x BDNF 相关的临床结果

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100 项与 TrkB x TrkA x p75NTR x BDNF 相关的转化医学

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0 项与 TrkB x TrkA x p75NTR x BDNF 相关的专利（医药）

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项与 TrkB x TrkA x p75NTR x BDNF 相关的文献（医药）

2024-07-01·Histology and histopathology

Differential roles of serotonin receptor subtypes in regulation of neurotrophin receptor expression and intestinal hypernociception.

Article

作者: Wu, Ming-Shiang ; Lin, Li-Yu ; Tu, Chia-Hung ; Hsin, Ling-Wei ; Hsieh, Yu-Ting ; Yu, Linda Chia-Hui ; She, Meng-Ping

OBJECTIVESAberrant serotonin (5-hydroxytryptamine, 5-HT) metabolism and neurite outgrowth were associated with abdominal pain in irritable bowel syndrome (IBS). We previously demonstrated that 5-HT receptor subtype 7 (5-HT₇) was involved in visceral hypersensitivity of IBS-like mouse models. The aim was to compare the analgesic effects of a novel 5-HT₇ antagonist to reference standards in mouse models and investigate the mechanisms of 5-HT₇-dependent neuroplasticity.METHODSTwo mouse models, including Giardia post-infection combined with water avoidance stress (GW) and post-resolution of trinitrobenzene sulfonic acid-induced colitis (PT) were used. Mice were orally administered CYY1005 (CYY, a novel 5-HT₇ antagonist), alosetron (ALN, a 5-HT₃ antagonist), and loperamide (LPM, an opioid receptor agonist) prior to measurement of visceromotor responses (VMR). Levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin receptors (NTRs) were assessed.RESULTSPeroral CYY was more potent than ALN or LPM in reducing VMR values in GW and PT mice. Increased mucosal 5-HT₇-expressing nerve fibers were associated with elevated Gap43 levels in the mouse colon. We observed higher colonic Ntrk2 and Ngfr expression in GW mice, and increased Bdnf expression in PT mice compared with control mice. Human SH-SY5Y cells stimulated with mouse colonic supernatant or exogenous serotonin exhibited longer nerve fibers, which CYY dose-dependently inhibited. Serotonin increased Ntrk1 and Ngfr expression via 5-HT₇ but not 5-HT₃ or 5-HT₄, while Ntrk2 upregulation was dependent on all three 5-HT receptor subtypes.CONCLUSIONSStronger analgesic effects by peroral CYY were observed compared with reference standards in two IBS-like mouse models. The 5-HT₇-dependent NTR upregulation and neurite elongation may be involved in intestinal hypernociception.

2023-11-01·Cellular and Molecular Neurobiology

Candidate Key Proteins in Tinnitus: A Bioinformatic Study of Synaptic Transmission in Spiral Ganglion Neurons

Article

作者: Knipper, Marlies ; Mazurek, Birgit ; Gross, Johann

AbstractTo study key proteins associated with changes in synaptic transmission in the spiral ganglion in tinnitus, we build three gene lists from the GeneCard database: 1. Perception of sound (PoS), 2. Acoustic stimulation (AcouStim), and 3. Tinnitus (Tin). Enrichment analysis by the DAVID database resulted in similar Gene Ontology (GO) terms for cellular components in all gene lists, reflecting synaptic structures known to be involved in auditory processing. The STRING protein–protein interaction (PPI) network and the Cytoscape data analyzer were used to identify the top two high-degree proteins (HDPs) and their high-score interaction proteins (HSIPs) identified by the combined score (CS) of the corresponding edges. The top two protein pairs (key proteins) for the PoS are BDNF-GDNF and OTOF-CACNA1D and for the AcouStim process BDNF-NTRK2 and TH-CALB1. The Tin process showed BDNF and NGF as HDPs, with high-score interactions with NTRK1 and NGFR at a comparable level. Compared to the PoS and AcouStim process, the number of HSIPs of key proteins (CS > 90. percentile) increases strongly in Tin. In the PoS and AcouStim networks, BDNF receptor signaling is the dominant pathway, and in the Tin network, the NGF-signaling pathway is of similar importance. Key proteins and their HSIPs are good indicators of biological processes and of signaling pathways characteristic for the normal hearing on the one hand and tinnitus on the other.Graphical Abstract

2022-08-01·Molecular Neurobiology

Interactions Among Brain-Derived Neurotrophic Factor and Neuroimmune Pathways Are Key Components of the Major Psychiatric Disorders

Review

作者: Gevezova, Maria ; Mehterov, Nikolay ; Maes, Michael ; Minchev, Danail ; Sarafian, Victoria

The purpose of this review is to summarize the current knowledge regarding the reciprocal associations between brain-derived neurotrophic factor (BDNF) and immune-inflammatory pathways and how these links may explain the involvement of this neurotrophin in the immune pathophysiology of mood disorders and schizophrenia. Toward this end, we delineated the protein-protein interaction (PPI) network centered around BDNF and searched PubMed, Scopus, Google Scholar, and Science Direct for papers dealing with the involvement of BDNF in the major psychosis, neurodevelopment, neuronal functions, and immune-inflammatory and related pathways. The PPI network was built based on the significant interactions of BDNF with neurotrophic (NTRK2, NTF4, and NGFR), immune (cytokines, STAT3, TRAF6), and cell-cell junction (CTNNB, CDH1) DEPs (differentially expressed proteins). Enrichment analysis shows that the most significant terms associated with this PPI network are the tyrosine kinase receptor (TRKR) and Src homology region two domain-containing phosphatase-2 (SHP2) pathways, tyrosine kinase receptor signaling pathways, positive regulation of kinase and transferase activity, cytokine signaling, and negative regulation of the immune response. The participation of BDNF in the immune response and its interactions with neuroprotective and cell-cell adhesion DEPs is probably a conserved regulatory process which protects against the many detrimental effects of immune activation and hyperinflammation including neurotoxicity. Lowered BDNF levels in mood disorders and schizophrenia (a) are associated with disruptions in neurotrophic signaling and activated immune-inflammatory pathways leading to neurotoxicity and (b) may interact with the reduced expression of other DEPs (CTNNB1, CDH1, or DISC1) leading to multiple aberrations in synapse and axonal functions.