Please use this identifier to cite or link to this item:
Title: Cdk5/p25-induced cytosolic PLA2-mediated lysophosphatidylcholine production regulates neuroinflammation and triggers neurodegeneration
Authors: Sundaram, J.R.
Chan, E.S.
Poore, C.P.
Pareek, T.K.
Cheong, W.F.
Shui, G. 
Tang, N.
Low, C.-M.
Wenk, M.R.
Kesavapany, S.
Issue Date: 18-Jan-2012
Citation: Sundaram, J.R., Chan, E.S., Poore, C.P., Pareek, T.K., Cheong, W.F., Shui, G., Tang, N., Low, C.-M., Wenk, M.R., Kesavapany, S. (2012-01-18). Cdk5/p25-induced cytosolic PLA2-mediated lysophosphatidylcholine production regulates neuroinflammation and triggers neurodegeneration. Journal of Neuroscience 32 (3) : 1020-1034. ScholarBank@NUS Repository.
Abstract: The deregulation of cyclin-dependent kinase 5 (Cdk5) by p25 has been shown to contribute to the pathogenesis in a number of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD). In particular, p25/Cdk5 has been shown to produce hyperphosphorylated tau, neurofibrillary tangles as well as aberrant amyloid precursor protein processing found in AD. Neuroinflammation has been observed alongside the pathogenic process in these neurodegenerative diseases, however the precise mechanism behind the induction of neuroinflammation and the significance in the AD pathogenesis has not been fully elucidated. In this report, we uncover a novel pathway for p25-induced neuroinflammation where p25 expression induces an early trigger of neuroinflammation in vivo in mice. Lipidomic mass spectrometry, in vitro coculture and conditioned media transfer experiments show that the soluble lipid mediator lysophosphatidylcholine (LPC) is released by p25 overexpressing neurons to initiate astrogliosis, neuroinflammation and subsequent neurodegeneration. Reverse transcriptase PCR and gene silencing experiments show that cytosolic phospholipase 2 (cPLA2) is the key enzyme mediating the p25-induced LPC production and cPLA2 upregulation is critical in triggering the p25-mediated inflammatory and neurodegenerative process. Together, our findings delineate a potential therapeutic target for the reduction of neuroinflammation in neurodegenerative diseases including AD. © 2012 the authors.
Source Title: Journal of Neuroscience
ISSN: 02706474
DOI: 10.1523/JNEUROSCI.5177-11.2012
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.


checked on Apr 2, 2020


checked on Mar 17, 2020

Page view(s)

checked on Mar 28, 2020

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.