PLEKHA1

Last update 08 May 2025

Basic Info

Synonyms

PH domain-containing family A member 1, pleckstrin homology domain containing A1, Pleckstrin homology domain-containing family A member 1

+ [4]

Introduction

Binds specifically to phosphatidylinositol 3,4-diphosphate (PtdIns3,4P2), but not to other phosphoinositides. May recruit other proteins to the plasma membrane.

100 Clinical Results associated with PLEKHA1

100 Translational Medicine associated with PLEKHA1

0 Patents (Medical) associated with PLEKHA1

Literatures (Medical) associated with PLEKHA1

01 Jun 2025·International Dental Journal

HDAC9-Mediated Pyroptosis Promotes Orthodontically Induced Inflammatory Root Resorption

Article

Author: Hu, Bingxue ; Huang, Junhao ; Ai, Hong ; Lin, Tianwei ; Mai, Zhihui ; Liu, Limin ; Lu, Hongfei ; Chen, Lin

INTRODUCTION AND AIMSOrthodontically induced inflammatory root resorption (OIIRR) is a common iatrogenic outcome of orthodontic treatment. Both epigenetic modifications and pyroptosis have demonstrated a certain role in OIIRR. This study aims to investigate whether epigenetic modifications regulate pyroptosis to be involved in OIIRR.METHODRat model of OIIRR was established, and the periodontal tissues were utilized for H&E staining, TRAP staining, immunofluorescence, transcriptome sequencing, and RT-qPCR analysis. Human periodontal ligament fibroblasts (hPDLFs) were overexpressed with HDAC9, treated with pyroptosis inhibitor, incubated with osteoclast, and then subjected to CUT&Tag sequencing.RESULTSOrthodontic force increased the distance of orthodontic tooth movement and the abundance of osteoclast. Transcriptome sequencing identified that Hdac9 was upregulated in the periodontal tissues of OIIRR rats compared to the control. Immunofluorescence revealed that HDAC9 was present in periodontal ligament fibroblasts, with reduced fluorescence of HDAC9 in OIIRR compared to the control. HDAC9 overexpression in hPDLFs induced pyroptosis and promoted osteoclast differentiation. These effects were reversed by pyroptosis inhibitor. CUT&Tag analysis showed that HDAC9 overexpression resulted in an enrichment of deacetylated genes on mitochondrial dysfunction-associated pathways. CUT&Tag-PCR analysis confirmed reduced H3K9ac enrichment on the mitochondrial dysfunction-associated genes VPS13D, AQP1, PEX2, CDK1, and PLEKHA1 after HDAC9 overexpression, and RT-qPCR analysis revealed a corresponding decrease in their respective expression levels. Accordingly, the ROS level was also increased by HDAC9 overexpression.CONCLUSIONHDAC9-mediated histone deacetylation induces mitochondrial dysfunction and pyroptosis in hPDLFs, thereby promoting osteoclast differentiation and OIIRR progression.CLINICAL RELEVANCEThis study reveals the regulatory mechanism of pyroptosis in OIIRR from the perspective of epigenetic modifications, providing new insights into the pathogenesis of OIIRR.

06 Mar 2025·Brain

Human longevity and Alzheimer’s disease variants act via microglia and oligodendrocyte gene networks

Article

Author: Escott-Price, Valentina ; Magusali, Naciye ; Rambarack, Naiomi ; Yaman, Umran ; Hardy, John ; Botia, Juan A ; Graham, Andrew C ; Sala Frigerio, Carlo ; Salih, Dervis A ; Celikag, Meral ; Harwood, Janet C ; Bellou, Eftychia

AbstractAgeing underlies functional decline of the brain and is the primary risk factor for several neurodegenerative conditions, including Alzheimer’s disease (AD). However, the molecular mechanisms that cause functional decline of the brain during ageing, and how these contribute to AD pathogenesis, are not well understood.The objective of this study was to identify biological processes that are altered during ageing in the hippocampus and that modify Ad risk and lifespan, and then to identify putative gene drivers of these programmes. We integrated common human genetic variation associated with human lifespan or Ad from genome-wide association studies with co-expression transcriptome networks altered with age in the mouse and human hippocampus.Our work confirmed that genetic variation associated with Ad was enriched in gene networks expressed by microglia responding to ageing and revealed that they were also enriched in an oligodendrocytic gene network. Compellingly, longevity-associated genetic variation was enriched in a gene network expressed by homeostatic microglia whose expression declined with age. The genes driving this enrichment include CASP8 and STAT3, highlighting a potential role for these longevity-associated genes in the homeostatic functions of innate immune cells, and these genes might drive ‘inflammageing’. Thus, we observed that gene variants contributing to ageing and AD balance different aspects of microglial and oligodendrocytic function. Furthermore, we also highlight putative Ad risk genes, such as LAPTM5, ITGAM and LILRB4, whose association with Ad falls below genome-wide significance but show strong co-expression with known Ad risk genes in these networks. Indeed, five of the putative risk genes highlighted by our analysis, ANKH, GRN, PLEKHA1, SNX1 and UNC5CL, have subsequently been identified as genome-wide significant risk genes in a subsequent genome-wide association study with larger sample size, validating our analysis.This work identifies new genes that influence ageing and AD pathogenesis, and highlights the importance of microglia and oligodendrocytes in the resilience of the brain against ageing and AD pathogenesis. Our findings have implications for developing markers indicating the physiological age of the brain and new targets for therapeutic intervention.

01 Feb 2025·Nature Genetics

Multi-omic quantitative trait loci link tandem repeat size variation to gene regulation in human brain

Article

Author: Thompson, Leslie M ; Li, Jason Sheng ; Li, Wei ; La Spada, Albert R ; Michels, Sebastian ; Philippe, Julien ; Colwin, Michael R ; Wu, Jie ; Sallam, Tamer ; Chen, Chaorong ; Cui, Ya ; Wang, Dan ; Arnold, Frederick J

Tandem repeat (TR) size variation is implicated in ~50 neurological disorders, yet its impact on gene regulation in the human brain remains largely unknown. In the present study, we quantified the impact of TR size variation on brain gene regulation across distinct molecular phenotypes, based on 4,412 multi-omics samples from 1,597 donors, including 1,586 newly sequenced ones. We identified ~2.2 million TR molecular quantitative trait loci (TR-xQTLs), linking ~139,000 unique TRs to nearby molecular phenotypes, including many known disease-risk TRs, such as the G₂C₄ expansion in C9orf72 associated with amyotrophic lateral sclerosis. Fine-mapping revealed ~18,700 TRs as potential causal variants. Our in vitro experiments further confirmed the causal and independent regulatory effects of three TRs. Additional colocalization analysis indicated the potential causal role of TR variation in brain-related phenotypes, highlighted by a 3'-UTR TR in NUDT14 linked to cortical surface area and a TG repeat in PLEKHA1, associated with Alzheimer's disease.

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PLEKHA1

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