开辟神经精神疾病治疗的新途径:过氧化物酶体增殖激活受体作为有前途的治疗靶点的新兴潜力。

IF 3.5 3区 医学 Q2 NEUROSCIENCES Psychopharmacology Pub Date : 2024-08-01 Epub Date: 2024-05-27 DOI:10.1007/s00213-024-06617-6
Asmita Deka Dey, Ashi Mannan, Sonia Dhiman, Thakur Gurjeet Singh
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引用次数: 0

摘要

理由过氧化物酶体增殖激活受体(PPARs)是一种转录因子,可调节炎症、脂质代谢和葡萄糖稳态等多种生理过程。最近的研究表明,以 PPAR 为靶点可以通过调节大脑神经元功能和信号通路来治疗神经精神疾病。研究发现,PPAR-α、PPAR-δ 和 PPAR-γ 在认知功能、神经炎症和神经保护中发挥着重要作用。PPAR 的失调与双相情感障碍、精神分裂症、重度抑郁障碍和自闭症谱系障碍等神经精神疾病有关。目前治疗方法的局限性和副作用促使研究人员将 PPARs 作为一种有前景的新型治疗策略。临床前和临床研究表明,PPAR 激动剂和拮抗剂具有改善这些疾病相关症状的潜力:本综述旨在概述目前对神经精神疾病中 PPARs 的认识、其作为治疗靶点的潜力以及开发基于 PPAR 的疗法所面临的挑战和未来方向:以 "PPAR、神经精神障碍、氧化应激、炎症、双相情感障碍、精神分裂症、重度抑郁障碍、自闭症谱系障碍、分子途径 "为关键词,对PubMed、Medline、Bentham、Scopus和EMBASE(Elsevier)数据库等多个搜索引擎进行了广泛的文献综述:尽管PPARs为神经精神疾病的创新治疗方法提供了一个充满希望的方向,但要解决障碍并将这种潜力转化为临床可行的个性化治疗方法,还需要开展更多的研究。
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Unlocking new avenues for neuropsychiatric disease therapy: the emerging potential of Peroxisome proliferator-activated receptors as promising therapeutic targets.

Rationale: Peroxisome proliferator-activated receptors (PPARs) are transcription factors that regulate various physiological processes such as inflammation, lipid metabolism, and glucose homeostasis. Recent studies suggest that targeting PPARs could be beneficial in treating neuropsychiatric disorders by modulating neuronal function and signaling pathways in the brain. PPAR-α, PPAR-δ, and PPAR-γ have been found to play important roles in cognitive function, neuroinflammation, and neuroprotection. Dysregulation of PPARs has been associated with neuropsychiatric disorders like bipolar disorder, schizophrenia, major depression disorder, and autism spectrum disorder. The limitations and side effects of current treatments have prompted research to target PPARs as a promising novel therapeutic strategy. Preclinical and clinical studies have shown the potential of PPAR agonists and antagonists to improve symptoms associated with these disorders.

Objective: This review aims to provide an overview of the current understanding of PPARs in neuropsychiatric disorders, their potential as therapeutic targets, and the challenges and future directions for developing PPAR-based therapies.

Methods: An extensive literature review of various search engines like PubMed, Medline, Bentham, Scopus, and EMBASE (Elsevier) databases was carried out with the keywords "PPAR, Neuropsychiatric disorders, Oxidative stress, Inflammation, Bipolar Disorder, Schizophrenia, Major depression disorder, Autism spectrum disorder, molecular pathway".

Result & conclusion: Although PPARs present a hopeful direction for innovative therapeutic approaches in neuropsychiatric conditions, additional research is required to address obstacles and convert this potential into clinically viable and individualized treatments.

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来源期刊
Psychopharmacology
Psychopharmacology 医学-精神病学
CiteScore
7.10
自引率
5.90%
发文量
257
审稿时长
2-4 weeks
期刊介绍: Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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