Abstract
Over the last decade, it has become evident that 14-3-3 proteins are essential for primary cell functions. These proteins are abundant throughout the body, including the central nervous system and interact with other proteins in both cell cycle and apoptotic pathways. Examination of cerebral spinal fluid in humans suggests that 14-3-3s including 14-3-3ε (YWHAE) are up-regulated in several neurological diseases, and loss or duplication of the YWHAE gene leads to Miller–Dieker syndrome. The goal of this review is to examine the utility of 14-3-3s as a marker of human immune deficiency virus (HIV)-dependent neurodegeneration and also as a tool to track disease progression. To that end, we describe mechanisms implicating 14-3-3s in neurological diseases and summarize evidence of its interactions with HIV accessory and co-receptor proteins.
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Abbreviations
- ACD:
-
AIDS dementia complex
- AD:
-
Alzheimer's disease
- ADHD:
-
Attention deficient hyperactivity disorder
- AIDS:
-
Acquired immunodeficiency virus
- BAD:
-
B-cell lymphoma 2 antagonist of cell death
- Bax:
-
Bcl-2-associated X
- BBB:
-
Blood–brain barrier
- Bcl-XL:
-
B-cell lymphoma-extra large
- C. elegans :
-
Caenorhabditis elegans
- Cdc25:
-
Cell division cycle phosphatase 25
- CDKs:
-
Cyclin-dependent protein kinases
- CJD:
-
Creutzfeldt–Jakob disease
- CME:
-
Cytomegalovirus encephalitis
- CNS:
-
Central nervous system
- CRK:
-
Viral oncogene causes increased tyrosine-phosphorylated proteins
- CSF:
-
Cerebral spinal fluid
- CXCR4:
-
CXC chemokine receptor 4
- DCAF-1:
-
DNA binding protein 1 and Cullin 4a-associated factor
- FoxO:
-
Forkhead transcription factor
- Gp120:
-
Glycoprotein 120
- GPR15:
-
G protein receptor 15
- GPRs:
-
G protein cell receptors
- HAD:
-
HIV-associated dementia
- HADC:
-
HIV-associated dementia complex
- HAND:
-
HIV-associated neurocognitive disorders
- HBMECs:
-
Human brain microvascular endothelial cells
- HCV:
-
Hepatitis C virus
- HEK293:
-
Human embryonic kidney
- Hela:
-
Human cervical carcinoma
- HepG2:
-
Human hepatoma
- HIV:
-
Human immune deficiency virus
- HIVE:
-
HIV encephalitis
- HMC:
-
Human mesangial growth cells
- HUVEC:
-
Human umbilical vein endothelial cells
- IL:
-
Interleukin
- ILK:
-
Isolated lissencephaly
- K2P:
-
Potassium channel
- LB:
-
Lewy bodies
- LIS1:
-
Encodes subunit of platelet-activating factor acetylhydrolase 1B (PAFAH1B1)
- MDS:
-
Miller–Dieker syndrome
- MS:
-
Multiple sclerosis
- MYO1C:
-
Myosin-1C
- Nef:
-
Negative factor
- PKA:
-
Protein kinase A
- PKC:
-
Protein kinase C
- Raf:
-
Proto-oncogene serine/threonine-protein kinase
- RNAi:
-
RNA interference
- S. pombe :
-
Schizosaccharomyces pombe
- siRNA:
-
Single stranded RNA\
- SIV:
-
Simian immunodeficiency virus
- TAU:
-
Tubulin-associated unit
- TUSC5:
-
Tumor suppressor candidate 5
- Vpr:
-
Viral protein R
- Vpu:
-
Viral protein U
- Ywhae −/− :
-
Ywhae/14-3-3ε-deficient mice
- YWHEA:
-
14-3-3ε (human gene)
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Acknowledgements
The study was funded by the National Center for Research Resources (NCRR) grant 1U54RR026139-01A1 (awarded to the University of Puerto Rico-Medical Science Campus). This publication (journal article, etc.) was supported by a grant from the Johns Hopkins NIMH Center for Novel Therapeutics of HIV-associated Cognitive Disorders. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Johns Hopkins University or any grantor providing funds to its NIMH Center for Novel Therapeutics of HIV-associated Cognitive Disorders. With special thanks to Dr. Avindra Nath and Dr. Valerie Wojna. The study was partially supported by the National Institute of Neurological Disorders and Stroke (NINDS), grants S11NS46278 and U54NS43011 (SNRP). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NCRR, NIMH, or NINDS. We acknowledge the support of Tirtsa Porrata-Doria and the Molecular Biology Core Lab of the Ponce School of Medicine and Health Sciences (grant RR003050). Special thanks go to Robert Ritchie of the RCMI/Ponce School of Medicine and Health Sciences Publications Office (G12 RR003050) for editing services.
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The authors have no conflicts of interest to disclose. The authors alone are responsible for the content and writing of the paper.
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Morales, D., Skoulakis, E.C.M. & Acevedo, S.F. 14-3-3s are potential biomarkers for HIV-related neurodegeneration. J. Neurovirol. 18, 341–353 (2012). https://doi.org/10.1007/s13365-012-0121-2
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DOI: https://doi.org/10.1007/s13365-012-0121-2