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FKBP immunophilins and Alzheimer’s disease: A chaperoned affair

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Abstract

The FK506-binding protein (FKBP) family of immunophilins consists of proteins with a variety of protein–protein interaction domains and versatile cellular functions. Analysis of the functions of immunophilins has been the focus of studies in recent years and has led to the identification of various molecular pathways in which FKBPs play an active role. All FKBPs contain a domain with prolyl cis/trans isomerase (PPIase) activity. Binding of the immunosuppressant molecule FK506 to this domain inhibits their PPIase activity while mediating immune suppression through inhibition of calcineurin. The larger members, FKBP51 and FKBP52, interact with Hsp90 and exhibit chaperone activity that is shown to regulate steroid hormone signalling. From these studies it is clear that FKBP proteins are expressed ubiquitously but show relatively high levels of expression in the nervous system. Consistent with this expression, FKBPs have been implicated with both neuroprotection and neurodegeneration. This review will focus on recent studies involving FKBP immunophilins in Alzheimer’s-disease-related pathways.

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Abbreviations

AD:

Alzheimer’s disease

AICD:

amyloid intracellular domain

APP:

amyloid precursor protein

FKBD:

FK506-binding domain

FKBP:

FK506-binding protein

FTDP:

fronto-temporal dementia and Parkinsonism linked to chromosome 17

mTOR:

mammalian target of rapamycin

TPR:

tetratricopeptide

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Acknowledgements

We would like to thank Drs R Buono and H Basehore (Golden Brain Bank, Coatsville VA Medical Center) for curating and providing the human brain samples, and our collaborator Dr R Birge for inspiration and exchange of ideas. This work was supported by internal funds from the Genetics Department, Rutgers University.

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Authors and Affiliations

  1. Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA

    Weihuan Cao & Mary Konsolaki

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  1. Weihuan Cao
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  2. Mary Konsolaki
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Correspondence to Mary Konsolaki.

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[Cao W and Konsolaki M 2011 FKBP immunophilins and Alzheimer’s disease: A chaperoned affair. J. Biosci. 36 493–498] DOI 10.1007/s12038-011-9080-7

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Cao, W., Konsolaki, M. FKBP immunophilins and Alzheimer’s disease: A chaperoned affair. J Biosci 36, 493–498 (2011). https://doi.org/10.1007/s12038-011-9080-7

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