Abstract |
Deletion of cellular isoform of prion protein (PrP(C)) increases neuronal predisposition to damage by modulating apoptosis and the negative consequences of oxidative stress. In vivo studies have demonstrated that PrP(C)-deficient mice are more prone to seizure, depression, and induction of epilepsy and experience extensive cerebral damage following ischemic challenge or viral infection. In addition, adenovirus-mediated overexpression of PrP(C) reduces brain damage in rat models of cerebral ischemia. In experimental autoimmune encephalomyelitis, PrP(C)-deficient mice reportedly have a more aggressive disease onset and less clinical improvement during the chronic phase than wild-type mice mice. In mice given oral dextran sulfate, PrP(C) has a potential protective role against inflammatory bowel disease. PrP(C)-deficient mice demonstrate significantly greater increases in blood glucose concentrations after intraperitoneal injection of glucose than wild-type mice. Further in vivo challenges to PrP gene-deficient models and conditional knockout models with siRNA and in vivo administration of PrP-ligating agents may assist in refining knowledge of the lymphoid function of PrP(C) and predicting the effects of anti-PrP treatment on the immune system. Together, these findings indicate that PrP(C) may have multiple neuroprotective and anti-inflammatory roles, which explains why this protein is so widely expressed.
|
Authors | Takashi Onodera, Akikazu Sakudo, Hirokazu Tsubone, Shigeyoshi Itohara |
Journal | Microbiology and immunology
(Microbiol Immunol)
Vol. 58
Issue 7
Pg. 361-74
(Jul 2014)
ISSN: 1348-0421 [Electronic] Australia |
PMID | 24866463
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
|
Copyright | © 2014 The Societies and Wiley Publishing Asia Pty Ltd. |
Chemical References |
|
Topics |
- Animals
- Bacterial Infections
(genetics, immunology, metabolism)
- Brain Ischemia
(genetics, immunology, metabolism)
- Cardiovirus Infections
(genetics, immunology, metabolism)
- Colitis
(genetics, immunology, metabolism)
- Depression
(genetics, immunology, metabolism)
- Disease Models, Animal
- Disease Susceptibility
- Encephalomyelitis, Autoimmune, Experimental
(genetics, immunology, metabolism)
- Epilepsy
(genetics, immunology, metabolism)
- Gene Knockout Techniques
- Humans
- Immunity
(genetics)
- Mice
- Mice, Knockout
- Prions
(genetics, metabolism)
- RNA Interference
- Stress, Physiological
|