Deciphering the Role of Peroxisome Proliferator-activated Receptor α and Phosphodiesterase Type 5 Targets in Alzheimer's Disease.

IF 2.7 4区 医学 Q3 NEUROSCIENCES CNS & neurological disorders drug targets Pub Date : 2024-01-01 DOI:10.2174/1871527323666230904150841
Parnika M Sose, Pravin P Kale, Gaurav M Doshi
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Abstract

The most prevalent cause of dementia is Alzheimer's disease (AD). Although the global AD rate is on a constant rise, medical research is yet to find a cure for this neurological condition. Current available therapeutic drugs for AD treatment only provide symptomatic alleviation. Therefore, it is essential to establish effective AD treatment strategies in addressing clinical needs. The development of disease-modifying treatments for use in the disease's early stages and the advancement of symptomatic drugs principally used in the disease's later stages are priorities in AD research. Given that the etiology of AD is difficult to comprehend, using a multimodal therapy intervention that targets molecular targets of AD-related degenerative processes is a practical strategy to change the course of AD progression. The current review article discussed PPAR-α (Peroxisome proliferator-activated receptor-α) and PDE5 (Phosphodiesterase type 5) targets with evidence for their preclinical and clinical importance. Furthermore, we support the targets with AD-related processes, functions, and remedial measures. A unique synergistic method for treating AD may involve the beneficial combinatorial targeting of these two receptors. Furthermore, we reviewed different PDE chemical families in this research and identified PDE5 inhibitors as one of the promising AD-related experimental and clinical disease-modifying medications. Lastly, we suggest jointly targeting these two pathways would be more beneficial than monotherapy in AD treatments.

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破译过氧化物酶体增殖激活受体α和磷酸二酯酶 5 型靶点在阿尔茨海默病中的作用
痴呆症最常见的病因是阿尔茨海默病(AD)。虽然全球阿尔茨海默病的发病率在持续上升,但医学研究仍未找到治愈这种神经系统疾病的方法。目前现有的治疗药物只能缓解症状。因此,建立有效的注意力缺失症治疗策略以满足临床需求至关重要。开发用于疾病早期阶段的疾病改变治疗方法,以及改进主要用于疾病晚期阶段的对症药物,是注意力缺失症研究的重点。鉴于AD的病因难以理解,使用针对AD相关变性过程分子靶点的多模式疗法干预是改变AD进展过程的实用策略。本综述文章讨论了PPAR-α(过氧化物酶体增殖激活受体-α)和PDE5(5型磷酸二酯酶)靶点,并提供了其临床前和临床重要性的证据。此外,我们还支持这些靶点与注意力缺失症相关的过程、功能和补救措施。治疗 AD 的独特协同方法可能涉及这两种受体的有益组合靶点。此外,在这项研究中,我们回顾了不同的 PDE 化学家族,发现 PDE5 抑制剂是与 AD 相关的实验和临床疾病调节药物之一。最后,我们认为联合靶向这两种通路比单一疗法更有益于AD的治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
5.10
自引率
3.30%
发文量
158
审稿时长
6-12 weeks
期刊介绍: Aims & Scope CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. CNS & Neurological Disorders - Drug Targets publishes guest edited thematic issues written by leaders in the field covering a range of current topics of CNS & neurological drug targets. The journal also accepts for publication original research articles, letters, reviews and drug clinical trial studies. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal is essential reading for all pharmaceutical scientists involved in drug discovery and development.
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