Next Article in Journal
Microbubbles-Assisted Ultrasound Triggers the Release of Extracellular Vesicles
Next Article in Special Issue
The Role of Neurogenic Inflammation in Blood-Brain Barrier Disruption and Development of Cerebral Oedema Following Acute Central Nervous System (CNS) Injury
Previous Article in Journal
Design for Additive Bio-Manufacturing: From Patient-Specific Medical Devices to Rationally Designed Meta-Biomaterials
Previous Article in Special Issue
Chrysin Attenuates VCAM-1 Expression and Monocyte Adhesion in Lipopolysaccharide-Stimulated Brain Endothelial Cells by Preventing NF-κB Signaling
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessReview
Int. J. Mol. Sci. 2017, 18(8), 1608; doi:10.3390/ijms18081608

Finding a Balance between Protection and Pathology: The Dual Role of Perforin in Human Disease

1
Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN 55905, USA
2
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA
*
Author to whom correspondence should be addressed.
Received: 14 June 2017 / Revised: 20 July 2017 / Accepted: 20 July 2017 / Published: 25 July 2017
(This article belongs to the Special Issue Blood–Brain Barrier in CNS Injury and Repair)
View Full-Text   |   Download PDF [3852 KB, uploaded 25 July 2017]   |  

Abstract

Perforin is critical for controlling viral infection and tumor surveillance. Clinically, mutations in perforin are viewed as unfavorable, as lack of this pore-forming protein results in lethal, childhood disease, familial hemophagocytic lymphohistiocytosis type 2 (FHL 2). However, many mutations in the coding region of PRF1 are not yet associated with disease. Animal models of viral-associated blood–brain barrier (BBB) disruption and experimental cerebral malaria (ECM) have identified perforin as critical for inducing pathologic central nervous system CNS vascular permeability. This review focuses on the role of perforin in both protecting and promoting human disease. It concludes with a novel hypothesis that diversity observed in the PRF1 gene may be an example of selective advantage that protects an individual from perforin-mediated pathology, such as BBB disruption. View Full-Text
Keywords: perforin; familial hemophagocytic lymphohistiocytosis type 2; blood–brain barrier disruption; single nucleotide variants; selective advantage perforin; familial hemophagocytic lymphohistiocytosis type 2; blood–brain barrier disruption; single nucleotide variants; selective advantage
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Willenbring, R.C.; Johnson, A.J. Finding a Balance between Protection and Pathology: The Dual Role of Perforin in Human Disease. Int. J. Mol. Sci. 2017, 18, 1608.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top