Molecular Identification of Protein Kinase C Beta in Alzheimer's Disease

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2020 Nov 13

PMID 33186918

Citations 4

Authors

Zhike Zhou

Fenqin Chen

Shanshan Zhong

Yi Zhou

Rongwei Zhang

Kexin Kang

Xiaoqian Zhang

Ying Xu

Mei Zhao

Chuansheng Zhao

Affiliations

Soon will be listed here.

Abstract

The purpose of this study was to investigate the potential roles of protein kinase C beta (PRKCB) in the pathogenesis of Alzheimer's disease (AD). We identified 2,254 differentially expressed genes from 19,245 background genes in AD versus control as well as PRKCB-low versus high group. Five co-expression modules were constructed by weight gene correlation network analysis. Among them, the 1,222 genes of the turquoise module had the strongest relation to AD and those with low PRKCB expression, which were enriched in apoptosis, axon guidance, gap junction, Fc gamma receptor (FcγR)-mediated phagocytosis, mitogen-activated protein kinase (MAPK) and vascular endothelial growth factor (VEGF) signaling pathways. The intersection pathways of PRKCB in AD were determined, including gap junction, FcγR-mediated phagocytosis, MAPK and VEGF signaling pathways. Based on the performance evaluation of the area under the curve of 75.3%, PRKCB could accurately predict the onset of AD. Therefore, low expressions of PRKCB was a potential causative factor of AD, which might be involved in gap junction, FcγR-mediated phagocytosis, MAPK and VEGF signaling pathways.

Citing Articles

Single-microglia transcriptomic transition network-based prediction and real-world patient data validation identifies ketorolac as a repurposable drug for Alzheimer's disease.

Xu J, Song W, Xu Z, Danziger M, Karavani E, Zang C Alzheimers Dement. 2024; 21(1):e14373.

PMID: 39641322 PMC: 11782846. DOI: 10.1002/alz.14373.

Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline.

Duggan M, Peng Z, Sipila P, Lindbohm J, Chen J, Lu Y Nat Aging. 2024; 4(9):1263-1278.

PMID: 39143319 PMC: 11408246. DOI: 10.1038/s43587-024-00682-4.

Genome-Wide Gene-Set Analysis Identifies Molecular Mechanisms Associated with ALS.

Vasilopoulou C, McDaid-McCloskey S, McCluskey G, Duguez S, Morris A, Duddy W Int J Mol Sci. 2023; 24(4).

PMID: 36835433 PMC: 9966913. DOI: 10.3390/ijms24044021.

The Combination of Salidroside and Hedysari Radix Polysaccharide Inhibits Mitochondrial Damage and Apoptosis via the PKC/ERK Pathway.

Yang S, Wang L, Xie Z, Zeng Y, Xiong Q, Pei T Evid Based Complement Alternat Med. 2022; 2022:9475703.

PMID: 35795284 PMC: 9252633. DOI: 10.1155/2022/9475703.

Proteogenomics Reveals Orthologous Alternatively Spliced Proteoforms in the Same Human and Mouse Brain Regions with Differential Abundance in an Alzheimer's Disease Mouse Model.

da Silva E, Santos L, De Oliveira F, Freitas F, Parreira V, Geremias Dos Santos H Cells. 2021; 10(7).

PMID: 34201730 PMC: 8303486. DOI: 10.3390/cells10071583.

References

Mukhopadhyay D, Nagy J, Manseau E, Dvorak H . Vascular permeability factor/vascular endothelial growth factor-mediated signaling in mouse mesentery vascular endothelium. Cancer Res. 1998; 58(6):1278-84. View

Gottesman R, Schneider A, Albert M, Alonso A, Bandeen-Roche K, Coker L . Midlife hypertension and 20-year cognitive change: the atherosclerosis risk in communities neurocognitive study. JAMA Neurol. 2014; 71(10):1218-27. PMC: 4226067. DOI: 10.1001/jamaneurol.2014.1646. View

Bard F, Cannon C, Barbour R, Burke R, Games D, Grajeda H . Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat Med. 2000; 6(8):916-9. DOI: 10.1038/78682. View

Ueyama T, Lennartz M, Noda Y, Kobayashi T, Shirai Y, Rikitake K . Superoxide production at phagosomal cup/phagosome through beta I protein kinase C during Fc gamma R-mediated phagocytosis in microglia. J Immunol. 2004; 173(7):4582-9. DOI: 10.4049/jimmunol.173.7.4582. View

Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E . Alzheimer's disease. Lancet. 2011; 377(9770):1019-31. DOI: 10.1016/S0140-6736(10)61349-9. View

Forsberg M, Druid P, Zheng L, Stendahl O, Sarndahl E . Activation of Rac2 and Cdc42 on Fc and complement receptor ligation in human neutrophils. J Leukoc Biol. 2003; 74(4):611-9. DOI: 10.1189/jlb.1102525. View

Mootha V, Lindgren C, Eriksson K, Subramanian A, Sihag S, Lehar J . PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003; 34(3):267-73. DOI: 10.1038/ng1180. View

DeKosky S, Scheff S . Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Ann Neurol. 1990; 27(5):457-64. DOI: 10.1002/ana.410270502. View

Lin G, Brownsey R, MacLeod K . Regulation of mitochondrial aconitase by phosphorylation in diabetic rat heart. Cell Mol Life Sci. 2009; 66(5):919-32. PMC: 11131558. DOI: 10.1007/s00018-009-8696-3. View

10.

Yi C, Mei X, Ezan P, Mato S, Matias I, Giaume C . Astroglial connexin43 contributes to neuronal suffering in a mouse model of Alzheimer's disease. Cell Death Differ. 2016; 23(10):1691-701. PMC: 5041199. DOI: 10.1038/cdd.2016.63. View

11.

Lange C, Storkebaum E, Ruiz de Almodovar C, Dewerchin M, Carmeliet P . Vascular endothelial growth factor: a neurovascular target in neurological diseases. Nat Rev Neurol. 2016; 12(8):439-54. DOI: 10.1038/nrneurol.2016.88. View

12.

Tsui C, Martinez-Martin N, Gaya M, Maldonado P, Llorian M, Legrave N . Protein Kinase C-β Dictates B Cell Fate by Regulating Mitochondrial Remodeling, Metabolic Reprogramming, and Heme Biosynthesis. Immunity. 2018; 48(6):1144-1159.e5. PMC: 6015119. DOI: 10.1016/j.immuni.2018.04.031. View

13.

Fischer B, Schmoll H, Riederer P, Bauer J, Platt D, Popa-Wagner A . Complement C1q and C3 mRNA expression in the frontal cortex of Alzheimer's patients. J Mol Med (Berl). 1995; 73(9):465-71. DOI: 10.1007/BF00202265. View

14.

Di Marco L, Venneri A, Farkas E, Evans P, Marzo A, Frangi A . Vascular dysfunction in the pathogenesis of Alzheimer's disease--A review of endothelium-mediated mechanisms and ensuing vicious circles. Neurobiol Dis. 2015; 82:593-606. DOI: 10.1016/j.nbd.2015.08.014. View

15.

Newton A . Protein kinase C: perfectly balanced. Crit Rev Biochem Mol Biol. 2018; 53(2):208-230. PMC: 5901981. DOI: 10.1080/10409238.2018.1442408. View

16.

Pascale A, Amadio M, Govoni S, Battaini F . The aging brain, a key target for the future: the protein kinase C involvement. Pharmacol Res. 2007; 55(6):560-9. DOI: 10.1016/j.phrs.2007.04.013. View

17.

Kam T, Park H, Gwon Y, Song S, Kim S, Moon S . FcγRIIb-SHIP2 axis links Aβ to tau pathology by disrupting phosphoinositide metabolism in Alzheimer's disease model. Elife. 2016; 5. PMC: 5106215. DOI: 10.7554/eLife.18691. View

18.

Wan Q, Tang J, Han Y, Wang D . Co-expression modules construction by WGCNA and identify potential prognostic markers of uveal melanoma. Exp Eye Res. 2017; 166:13-20. DOI: 10.1016/j.exer.2017.10.007. View

19.

Patel N, Mathura V, Bachmeier C, Beaulieu-Abdelahad D, Laporte V, Weeks O . Alzheimer's beta-amyloid peptide blocks vascular endothelial growth factor mediated signaling via direct interaction with VEGFR-2. J Neurochem. 2009; 112(1):66-76. DOI: 10.1111/j.1471-4159.2009.06426.x. View

20.

Abrams S, Brown B, Zuzel M, Slupsky J . Vascular endothelial growth factor stimulates protein kinase CbetaII expression in chronic lymphocytic leukemia cells. Blood. 2010; 115(22):4447-54. DOI: 10.1182/blood-2009-06-229872. View