Down-regulation of cyclin D2 in amyloid β toxicity, inflammation, and Alzheimer's disease

Grzegorz A Czapski; Magdalena Cieślik; Emilia Białopiotrowicz; Walter J Lukiw; Joanna B Strosznajder

doi:10.1371/journal.pone.0259740

Down-regulation of cyclin D2 in amyloid β toxicity, inflammation, and Alzheimer's disease

PLoS One. 2021 Nov 18;16(11):e0259740. doi: 10.1371/journal.pone.0259740. eCollection 2021.

Authors

Grzegorz A Czapski¹, Magdalena Cieślik¹, Emilia Białopiotrowicz², Walter J Lukiw³, Joanna B Strosznajder¹

Affiliations

¹ Department of Cellular Signalling, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.
² Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, Warsaw, Poland.
³ LSU Neuroscience Center and Departments of Neurology and Ophthalmology, Louisiana State University School of Medicine, New Orleans, LA, United States of America.

Abstract

In the current study, we analyzed the effects of the systemic inflammatory response (SIR) and amyloid β (Aβ) peptide on the expression of genes encoding cyclins and cyclin-dependent kinase (Cdk) in: (i) PC12 cells overexpressing human beta amyloid precursor protein (βAPP), wild-type (APPwt-PC12), or carrying the Swedish mutantion (APPsw-PC12); (ii) the murine hippocampus during SIR; and (iii) Alzheimer's disease (AD) brain. In APPwt-PC12 expression of cyclin D2 (cD2) was exclusively reduced, and in APPsw-PC12 cyclins cD2 and also cA1 were down-regulated, but cA2, cB1, cB2, and cE1 were up-regulated. In the SIR cD2, cB2, cE1 were found to be significantly down-regulated and cD3, Cdk5, and Cdk7 were significantly up-regulated. Cyclin cD2 was also found to be down-regulated in AD neocortex and hippocampus. Our novel data indicate that Aβ peptide and inflammation both significantly decreased the expression of cD2, suggesting that Aβ peptides may also contribute to downregulation of cD2 in AD brain.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / metabolism*
Amyloid beta-Peptides / metabolism*
Animals
Cyclin D2 / metabolism*
Female
Humans
Inflammation / metabolism*
Mice
Mice, Inbred C57BL
Polymerase Chain Reaction

Substances

Amyloid beta-Peptides
Cyclin D2

Grants and funding

Research on amyloid neurotoxicity, inflammation, and microRNA signaling in AD and AD models was supported by the statutory budget (Theme No. 5) of the Mossakowski Medical Research Institute Polish Academy of Sciences awarded to GAC, MC, JBS. The study was also funded by an unrestricted grant from 'Research to Prevent Blindness' (RPB), an award from The Brown Foundation's Joe and Dorothy Dorsett Innovation in Science Healthy Aging Award given to WJL, a grant from the Louisiana Biotechnology Research Network (LBRN) given to WJL, and grants from the Alzheimer’s Disease Research Center (ADRC) at the UC Irvine Institute for Memory Impairments and Neurological Disorders (UCI MIND) funded by the NIA (UCI-ADRC; NIA AG16573) and NIH (Grant NEI EY006311, Grant NIA AG18031, Grant NIA AG038834) awarded to WJL. The funders had no role in the study design, data collection, and analysis, decision to publish, or preparation of the manuscript.