Delving into the Latest Updates on miCure Therapeutics Ltd with Synapse

概览

排名前五的药物类型	数量

miRNA	2

排名前五的靶点	数量

5-HT1A receptor x MIR135A1 x SERT	1

关联

2

项与 miCure Therapeutics Ltd 相关的药物

MIC-083

靶点

5-HT1A receptor x MIR135A1 x SERT

作用机制

5-HT1A receptor拮抗剂 [+2]

在研机构

miCure Therapeutics Ltd

原研机构

miCure Therapeutics Ltd

在研适应症

抑郁症

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-

miR-135

靶点-

作用机制-

在研机构

miCure Therapeutics Ltd

原研机构

miCure Therapeutics Ltd

在研适应症

重度抑郁症 [+1]

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-

100 项与 miCure Therapeutics Ltd 相关的临床结果

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0 项与 miCure Therapeutics Ltd 相关的专利（医药）

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5

项与 miCure Therapeutics Ltd 相关的文献（医药）

2024-05-01·iScience

ER stress in mouse serotonin neurons triggers a depressive phenotype alleviated by ketamine targeting eIF2α signaling

Article

作者: Miquel-Rio, Lluis ; Campa, Leticia ; Florensa-Zanuy, Eva ; Sancho-Alonso, María ; Sarriés-Serrano, Unai ; Pilar-Cuéllar, Fuencisla ; Bortolozzi, Analia ; Paz, Verónica ; Ruiz-Bronchal, Esther ; Manashirov, Sharon

Depression is a devastating mood disorder that causes significant disability worldwide. Current knowledge of its pathophysiology remains modest and clear biological markers are lacking. Emerging evidence from human and animal models reveals persistent alterations in endoplasmic reticulum (ER) homeostasis, suggesting that ER stress-related signaling pathways may be targets for prevention and treatment. However, the neurobiological basis linking the pathways involved in depression-related ER stress remains unknown. Here, we report that an induced model of ER stress in mouse serotonin (5-HT) neurons is associated with reduced Egr1-dependent 5-HT cellular activity and 5-HT neurotransmission, resulting in neuroplasticity deficits in forebrain regions and a depressive-like phenotype. Ketamine administration engages downstream eIF2α signaling to trigger rapid neuroplasticity events that rescue the depressive-like effects. Collectively, these data identify ER stress in 5-HT neurons as a cellular pathway involved in the pathophysiology of depression and show that eIF2α is critical in eliciting ketamine's fast antidepressant effects.

2022-06-01·STAR Protocols

Intracerebral administration of a modified antisense oligonucleotide targeting the dopamine system in a mouse model of Parkinson’s disease

Article

作者: Miquel-Rio, Lluis ; Campa, Leticia ; Bortolozzi, Analia ; Pavia-Collado, Rubén

Here, we present an optimized protocol for generating a mouse model overexpressing human α-synuclein in dopamine (DA) neurons driven by an adeno-associated viral (AAV) vector and for the examination of the benefit of an antisense oligonucleotide (ASO)-based therapy on DA neurotransmission under Parkinson's disease (PD)-like conditions. We describe AAV injection, followed by implantation of an osmotic minipump for ASO delivery and a guide cannula for microdialysis to measure DA release. This protocol can be used to evaluate oligonucleotide-based therapies for PD. For complete details on the use and execution of this protocol, please refer to Alarcón-Arís et al. (2020).

2021-11-01·Pharmacology & Therapeutics1区 · 医学

Oligonucleotides as therapeutic tools for brain disorders: Focus on major depressive disorder and Parkinson's disease

1区 · 医学

Review

作者: Bortolozzi, Analia ; Artigas, Francesc ; Chen, Alon ; Manashirov, Sharon

Remarkable advances in understanding the role of RNA in health and disease have expanded considerably in the last decade. RNA is becoming an increasingly important target for therapeutic intervention; therefore, it is critical to develop strategies for therapeutic modulation of RNA function. Oligonucleotides, including antisense oligonucleotide (ASO), small interfering RNA (siRNA), microRNA mimic (miRNA), and anti-microRNA (antagomir) are perhaps the most direct therapeutic strategies for addressing RNA. Among other mechanisms, most oligonucleotide designs involve the formation of a hybrid with RNA that promotes its degradation by activation of endogenous enzymes such as RNase-H (e.g., ASO) or the RISC complex (e.g. RNA interference - RNAi for siRNA and miRNA). However, the use of oligonucleotides for the treatment of brain disorders is seriously compromised by two main limitations: i) how to deliver oligonucleotides to the brain compartment, avoiding the action of peripheral RNAses? and once there, ii) how to target specific neuronal populations? We review the main molecular pathways in major depressive disorder (MDD) and Parkinson's disease (PD), and discuss the challenges associated with the development of novel oligonucleotide therapeutics. We pay special attention to the use of conjugated ligand-oligonucleotide approach in which the oligonucleotide sequence is covalently bound to monoamine transporter inhibitors (e.g. sertraline, reboxetine, indatraline). This strategy allows their selective accumulation in the monoamine neurons of mice and monkeys after their intranasal or intracerebroventricular administration, evoking preclinical changes predictive of a clinical therapeutic action after knocking-down disease-related genes. In addition, recent advances in oligonucleotide therapeutic clinical trials are also reviewed.

100 项与 miCure Therapeutics Ltd 相关的药物交易

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100 项与 miCure Therapeutics Ltd 相关的转化医学

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