The P21-Activated Kinase 1 and 2 As Potential Therapeutic Targets for the Management of Cardiovascular Disease

Xu, Hui; Wang, Dingwei; Ramponi, Chiara; Wang, Xin; Zhang, Hongyuan

doi:10.53941/ijddp.v1i1.179

Cited by 3 publications

(2 citation statements)

References 112 publications

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“…Group I p21-activated kinases (Paks) are members of the serine/threonine protein kinase family, are downstream effectors of Rac1 and Cdc42. Zhang et al from University of Manchester provide greater understanding of the structure, activation, and function of group I Paks, mainly Pak1 and Pak2 (Pak1/2), centring on their protective roles against cardiovascular disease [4]. Albeit Pak1/2 are historically regarded as oncogenes, however, the signalling programs regulating cell proliferation may be closely related to the programs that control growth of postmitotic adult cardiomyocytes.…”

Section: Editorialmentioning

confidence: 99%

“…Collectively, these findings confirm that Pak2 confers cardioprotective effects in several disease conditions. Owing to the role of Pak1/2 in the cardiovascular system, Zhang et al rationalise strategies activating Pak1 and Pak2 could be a promising avenue for drug development [4]. A case of repurposing Fingolimod (FTY720), an FDA-approved anti-multiple sclerosis drug, for cardiac applications of alleviating cardiac hypertrophy and ischemic injury was described.…”

Section: Editorialmentioning

confidence: 99%

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Current Progress in Drug Target Identification and Drug Delivery

Wang¹

2022

IJDDP

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Section: Editorialmentioning

confidence: 99%

Section: Editorialmentioning

confidence: 99%

Current Progress in Drug Target Identification and Drug Delivery

Wang¹

2022

IJDDP

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Regulation of Vascular Injury and Repair by P21-Activated Kinase 1 and P21-Activated Kinase 2: Therapeutic Potential and Challenges

Han,

Zhu,

Liu

et al. 2024

Biomolecules

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The PAK (p21-activated kinases) family is a class of intracellular signal transduction protein kinases that regulate various cellular functions, mainly through their interactions with small GTP enzymes. PAK1 and PAK2 in the PAK kinase family are key signal transduction molecules that play important roles in various biological processes, including morphological changes, migration, proliferation, and apoptosis, and are involved in the progression of many diseases. Abnormal expression or dysregulation of PAK1 and PAK2 may be associated with several diseases, including cancer, neurological diseases, etc. The current research mainly focuses on studying the role of PAK and PAK inhibitors in the regulation of cancer progression, but relatively few reports are available that explore their potential role in cardiovascular diseases. Vascular injury and repair are complex processes involved in many cardiovascular conditions, including atherosclerosis, restenosis, and hypertension. Emerging research suggests that PAK1 and PAK2 have pivotal roles in vascular endothelial cell functions, including migration, proliferation, and angiogenesis. These kinases also modulate vascular smooth muscle relaxation, vascular permeability, and structural alterations, which are critical in the development of atherosclerosis and vascular inflammation. By targeting these activities, PAK proteins are essential for both normal vascular physiology and the pathogenesis of vascular diseases, highlighting their potential as therapeutic targets for vascular health. This review focuses on recent studies that offer experimental insights into the mechanisms by which PAK1 and PAK2 regulate the biological processes of vascular injury and repair and the therapeutic potential of the current existing PAK inhibitors in vascular-related diseases. The limitations of treatment with some PAK inhibitors and the ways that future development can overcome these challenges are also discussed.

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p21-Activated Kinases Present a New Drug Target for Hypertrophic Cardiomyopathy

He,

Lei

2023

IJDDP

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Expert review p21-Activated Kinases Present a New Drug Target for Hypertrophic Cardiomyopathy He Yu , and Lei Ming , * Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK * Correspondence: ming.lei@pharm.ox.ac.uk Received: 17 February 2023 Accepted: 26 March 2023 Published: 21 August 2023 Abstract: Hypertrophic cardiomyopathy (HCM), primarily involving mutations in sarcomeric proteins, is the most common form of inherited heart disease and a leading cause of sudden death in young adults and athletes. HCM patients present with cardiac hypertrophy, fibrosis, and diastolic dysfunction often in a progressive manner. Despite significant progress made in understanding the molecular genetic basis of HCM, there remains a lack of effective and specific treatment for preventing disease progression in HCM. This article first provides an overview of recent progress in understanding the pathogenic basis of disease progression in HCM, in particular dysfunctional calcium handling, mitochondrial impairment, and endoplasmic reticulum stress. This article then analyses the evidence for critical roles of the multifunctional enzymes P21-activated kinase-1 and 2 (Pak1/2) in the heart and our opinion on their therapeutic value as a promising druggable target in pathological hypertrophy and associated ventricular arrhythmias.

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The P21-Activated Kinase 1 and 2 As Potential Therapeutic Targets for the Management of Cardiovascular Disease

Cited by 3 publications

References 112 publications

Current Progress in Drug Target Identification and Drug Delivery

Current Progress in Drug Target Identification and Drug Delivery

Regulation of Vascular Injury and Repair by P21-Activated Kinase 1 and P21-Activated Kinase 2: Therapeutic Potential and Challenges

p21-Activated Kinases Present a New Drug Target for Hypertrophic Cardiomyopathy

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