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14-3-3s are potential biomarkers for HIV-related neurodegeneration

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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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