Research Progress on Plk1 in Neurodegenerative Diseases

doi:10.3870/j.issn.1672-8009.2026.04.014

Abstract

Abstract: As a key member of the serine/threonine protein kinase family,Polo-like kinase 1(Plk1)is a core regulator of the cell cycle,whose dysfunction is closely related to tumorigenesis.Recent research has found that Plk1 is abnormally expressed in terminally differentiated neurons and is closely associated with the pathological processes of neurodegenerative diseases such as Alzheimer’s disease,Parkinson’s disease and amyotrophic lateral sclerosis.It is particularly noteworthy that Plk1 plays a dual role in diseases like Alzheimer’s:it not only directly mediates neuronal death by driving aberrant cell cycle re-entry but also participates in regulating neuroprotective processes such as autophagy.The complex role of Plk1 in neurodegenerative diseases,particularly its seemingly contradictory dual function,offers a new perspective for understanding the mechanisms underlying neurodegenerative disorders and developing novel therapeutic strategies.

Key words: Polo-like kinase 1, neurodegenerative diseases, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis

CLC Number:

CHEN Yurou, YU Nan, LI Wei. Research Progress on Plk1 in Neurodegenerative Diseases[J]. Journal of Medical Molecular Biology, 2026, 23(4): 466-470.

References

[1] KALOUS J,ALESHKINA D.Multiple roles of PLK1 in mitosis and meiosis[J].Cells,2023,12(1):187.
[2] ILIAKI S,BEYAERT R,AFONINA I S.Polo-like kinase 1(PLK1)signaling in cancer and beyond[J].Biochem Pharmacol,2021,193:114747.
[3] ALFARO E,LÓPEZ-JIMÉNEZ P,GONZÁLEZ-MARTÍ-NEZ J,et al.PLK1 regulates centrosome migration and spindle dynamics in male mouse meiosis[J].EMBO Rep,2021,22(4):e51030.
[4] ADRIAANS I E,BASANT A,PONSIOEN B,et al.PLK1 plays dual roles in centralspindlin regulation during cytokinesis[J].J Cell Biol,2019,218(4):1250-1264.
[5] LI Z,LI J,KONG Y,et al.Plk1 phosphorylation of Mre11 antagonizes the DNA damage response[J].Cancer Res,2017,77(12):3169-3180.
[6] CHEN L L,WANG Y B,SONG J X,et al.Phosphoproteome-based kinase activity profiling reveals the critical role of MAP2 K2 and PLK1 in neuronal autophagy[J].Autophagy,2017,13(11):1969-1980.
[7] REDA M,NGAMCHERDTRAKUL W,NELSON M A,et al.Development of a nanoparticle-based immunotherapy targeting PD-L1 and PLK1 for lung cancer treatment[J].Nat Commun,2022,13(1):4261.
[8] GONZÁLEZ-MARTÍNEZ J,CWETSCH A W,GILABERT-JUAN J,et al.Genetic interaction between PLK1 and downstream MCPH proteins in the control of centrosome asymmetry and cell fate during neural progenitor division[J].Cell Death Differ,2022,29(8):1474-1485.
[9] SONG B,DAVIS K,LIU X S,et al.Inhibition of Polo-like kinase 1 reduces beta-amyloid-induced neuronal cell death in Alzheimer’s disease[J].Aging,2011,3(9):846-851.
[10] SZEWCZYK B,ZIMYANIN V,JAPTOK J,et al.Activation of polo-like kinase 1 correlates with selective motor neuron vulnerability in familial ALS[J].Cell Rep,2025,44(9):116113.
[11] ARCHAMBAULT V,LÉPINE G,KACHANER D.Understanding the polo kinase machine[J].Oncogene,2015,34(37):4799-4807.
[12] SEKI A,COPPINGER J A,JANG C Y,et al.Boraand the kinase Aurora a cooperatively activate the kinase Plk1 and control mitotic entry[J].Science,2008,320(5883):1655-1658.
[13] LINDON C,PINES J.Ordered proteolysis in anaphase inactivates Plk1 to contribute to proper mitotic exit in human cells[J].J Cell Biol,2004,164(2):233-241.
[14] LOWERY D M,LIM D,YAFFE M B.Structure and function of polo-like kinases[J].Oncogene,2005,24(2):248-259.
[15] XU J,SHEN C,WANG T,et al.Structural basis for the inhibition of polo-like kinase 1[J].Nat Struct Mol Biol,2013,20(9):1047-1053.
[16] ELIA A E,RELLOS P,HAIRE L F,et al.The molecular basis for phosphodependent substrate targeting and regulation of Plks by the Polo-box domain[J].Cell,2003,115(1):83-95.
[17] MBEFO M K,PALEOLOGOU K E,BOUCHARABA A,et al.Phosphorylation of synucleins by members of the Polo-like kinase family[J].J Biol Chem,2010,285(4):2807-2822.
[18] ROSTAGNO A A.Pathogenesis of Alzheimer’s disease[J].Int J Mol Sci,2022,24(1):107.
[19] SCHELTENS P,DE STROOPER B,KIVIPELTO M,et al.Alzheimer’s disease[J].Lancet,2021,397(10284):1577-1590.
[20] THAKUR S,DHAPOLA R,SARMA P,et al.Neuroinflammation in Alzheimer’s disease:Current progress in molecular signaling and therapeutics[J].Inflammation,2023,46(1):1-17.
[21] GRIFFITHS J,GRANT S G N.Synapse pathology in Alzheimer’s disease[J].Semin Cell Dev Biol,2023,139:13-23.
[22] ZHANG W,WANG J,ZHANG Y,et al.The scaffold protein TANK/I-TRAF inhibits NF-kappaB activation by recruiting polo-like kinase 1[J].Mol Biol Cell,2010,21(14):2500-2513.
[23] VITOUR D,DABO S,AHMADI POUR M,et al.Polo-like kinase 1(PLK1)regulates interferon(IFN)induction by MAVS[J].J Biol Chem,2009,284(33):21797-21809.
[24] YE H,ROBAK L A,YU M,et al.Genetics and pathogenesis of Parkinson’s syndrome[J].Annu Rev Pathol,2023,18:95-121.
[25] WANINGER S,BERKA C,STEVANOVIC KARIC M,et al.Neurophysiological biomarkers of Parkinson’s disease[J].J Parkinsons Dis,2020,10(2):471-480.
[26] WAXMAN E A,GIASSON B I.Characterization of kinases involved in the phosphorylation of aggregated α-synuclein[J].J Neurosci Res,2011,89(2):231-247.
[27] SATO H,ARAWAKA S,HARA S,et al.Authentically phosphorylated α-synuclein at Ser129 accelerates neurodegeneration in a rat model of familial Parkinson’s disease[J].J Neurosci,2011,31(46):16884-16894.
[28] RAMALINGAM N,DETTMER U.α-Synuclein serine129 phosphorylation-the physiology of pathology[J].Mol Neurodegener,2023,18(1):84.
[29] VAN HUMBEECK C,CORNELISSEN T,VANDENBERGHE W.Ambra1:a Parkin-binding protein involved in mitophagy[J].Autophagy,2011,7(12):1555-1556.
[30] VAN HUMBEECK C,CORNELISSEN T,HOFKENS H,et al.Parkin interacts with Ambra1 to induce mitophagy[J].J Neurosci,2011,31(28):10249-10261.
[31] SONG P,PENG W,SAUVE V,et al.Parkinson’s disease-linked parkin mutation disrupts recycling of synaptic vesicles in human dopaminergic neurons[J].Neuron,2023,111(23):3775-3788.e7.
[32] LEE S B,KIM J J,NAM H J,et al.Parkin regulates mitosis and genomic stability through Cdc20/Cdh1[J].Mol Cell,2015,60(1):21-34.
[33] MIKI Y,TANJI K,MORI F,et al.AMBRA1,a novel α-synuclein-binding protein,is implicated in the pathogenesis of multiple system atrophy[J].Brain Pathol,2018,28(1):28-42.
[34] FAIENZA F,POLVERINO F,RAJENDRAPRASAD G,et al.AMBRA1 phosphorylation by CDK1 and PLK1 regulates mitotic spindle orientation[J].Cell Mol Life Sci,2023,80(9):251.
[35] FELDMAN E L,GOUTMAN S A,PETRI S,et al.Amyotrophic lateral sclerosis[J].Lancet,2022,400(10360):1363-1380.
[36] NIJS M,VAN DAMME P.The genetics of amyotrophic lateral sclerosis[J].Curr Opin Neurol,2024,37(5):560-569.
[37] RIZEA R E,CORLATESCU A D,COSTIN H P,et al.Understanding amyotrophic lateral sclerosis:Pathophysiology,diagnosis,and therapeutic advances[J].Int J Mol Sci,2024,25(18):9966.
[38] YATA KLLOYD J,MASLEN S,et al.Plk1 and CK2 act in concert to regulate Rad51 during DNA double strand break repair[J].Mol Cell,2012,45(3):371-383.
[39] PENG B,SHI R,BIAN J,et al.PARP1 and CHK1 coordinate PLK1 enzymatic activity during the DNA damage response to promote homologous recombination-mediated repair[J].Nucleic Acids Res,2021,49(13):7554-7570.
[40] ZIMYANIN V,DASH B P,GROßMANN D,et al.Axonal transcriptome reveals upregulation of PLK1 as a protective mechanism in response to increased DNA damage in FUS^P525L spinal motor neurons[J].bioRxiv,2024:2024.11.20.624439.