RT Journal Article
ID 281898cb459a02d2
A1 Aloi, Macarena S.
A1 Su, Wei
A1 Garden, Gwenn A.
T1 The p53 Transcriptional Network Influences Microglia Behavior and Neuroinflammation
JF Critical Reviews™ in Immunology
JO CRI
YR 2015
FD 2016-01-29
VO 35
IS 5
SP 401
OP 415
K1 CNS ischemia
K1 inflammation
K1 macrophage
K1 microRNA
K1 neurodegeneration
AB The tumor-suppressor protein p53 belongs to a family of proteins that play pivotal roles in multiple
cellular functions including cell proliferation, cell death, genome stability, and regulation of inflammation. Neuroinflammation is a common feature of central nervous system (CNS) pathology, and microglia are the specialized
resident population of CNS myeloid cells that initiate innate immune responses. Microglia maintain CNS homeostasis
through pathogen containment, phagocytosis of debris, and initiation of tissue-repair cascades. However, an unregulated pro-inflammatory response can lead to tissue injury and dysfunction in both acute and chronic inflammatory states. Therefore, regulation of the molecular signals that control the induction, magnitude, and resolution of inflammation are necessary for optimal CNS health. We and others have described a novel mechanism by which p53 transcriptional activity modulates microglia behaviors in vitro and in vivo. Activation of p53 induces expression of microRNAs (miRNAs) that support microglia pro-inflammatory functions and suppress anti-inflammatory and tissue repair behaviors.
In this review, we introduce the previously described roles of the p53 signaling network and discuss novel
functions of p53 in the microglia-mediated inflammatory response in CNS health and disease. Ultimately, improved
understanding of the molecular regulators modulated by p53 transcriptional activity in microglia will enhance the
development of rational therapeutic strategies to harness the homeostatic and tissue repair functions of microglia.
PB Begell House
LK https://www.dl.begellhouse.com/journals/2ff21abf44b19838,3cf9880e7437a8b5,281898cb459a02d2.html