TY - JOUR
T1 - Finding a balance between protection and pathology
T2 - The dual role of perforin in human disease
AU - Willenbring, Robin C.
AU - Johnson, Aaron J.
N1 - Funding Information:
We would like to members of the Johnson Lab for careful reading of this manuscript. We would like to thank the following for funding this work: NIH R56 NS94150 and R01 NS103212. The funding agencies did not have any say in the design or interpretation of results in this study.
Publisher Copyright:
© 2017 by the authors.
PY - 2017/8
Y1 - 2017/8
N2 - 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.
AB - 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.
KW - Blood-brain barrier disruption
KW - Familial hemophagocytic lymphohistiocytosis type 2
KW - Perforin
KW - Selective advantage
KW - Single nucleotide variants
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U2 - 10.3390/ijms18081608
DO - 10.3390/ijms18081608
M3 - Review article
C2 - 28757574
AN - SCOPUS:85026362318
VL - 18
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 8
M1 - 1608
ER -