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Nuclear receptors in neural stem/progenitor cell homeostasis

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Abstract

In the central nervous system, embryonic and adult neural stem/progenitor cells (NSCs) generate the enormous variety and huge numbers of neuronal and glial cells that provide structural and functional support in the brain and spinal cord. Over the last decades, nuclear receptors and their natural ligands have emerged as critical regulators of NSC homeostasis during embryonic development and adult life. Furthermore, substantial progress has been achieved towards elucidating the molecular mechanisms of nuclear receptors action in proliferative and differentiation capacities of NSCs. Aberrant expression or function of nuclear receptors in NSCs also contributes to the pathogenesis of various nervous system diseases. Here, we review recent advances in our understanding of the regulatory roles of steroid, non-steroid, and orphan nuclear receptors in NSC fate decisions. These studies establish nuclear receptors as key therapeutic targets in brain diseases.

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Abbreviations

AADC:

Aromatic l-amino acid decarboxylase

Aβ:

Amyloid beta

AD:

Alzheimer’s disease

AGE:

Advanced glycated end

ALS:

Amyotrophic lateral sclerosis

APP:

Amyloid precursor protein

BBB:

Blood-brain barrier

BDNF:

Brain-derived neurotrophic factor

BPA:

Bisphenol A

Bxt:

Bexarotene

CA:

3α,7α,12α-Trihydroxy-5β-cholan-24-oic acid

CNS:

Central nervous system

CNTF:

Ciliary neurotrophic factor

COUP-TF:

Chicken ovalbumin upstream promoter-transcription factor

DA:

Dopaminergic

DAT:

Dopamine transporter

DBD:

DNA binding domain

DEX:

Dexamethasone

DG:

Dentate gyrus

DHA:

Docosahexaenoic acid

DVD:

Developmental vitamin D

E2:

17β-Estradiol

ER:

Estrogen receptor

ERE:

Estrogen response element

ESCs:

Embryonic stem cells

Ftz-F1:

Fushi tarazu factor 1

GC:

Glucocorticoid

GCNF:

Germ cell nuclear factor

GDNF:

Glial-derived neurotrophic factor

GJIC:

Gap junction intracellular communication

GR:

Glucocorticoid receptor

GRE:

Glucocorticoid response element

HDAC:

Histone deacetylase

HPA:

Hypothalamus–pituitary–adrenals

iPSCs:

Induced pluripotent stem cells

LBD:

Ligand-binding domain

LRH-1:

Liver receptor homolog 1

LXR:

Liver X receptor

MAP2:

Microtubule-associated protein 2

MR:

Minerolocorticoid receptor

MSCs:

Mesenchymal stem cells

NBRE:

NGFI-B response element

N-CoR:

Nuclear receptor co-repressor

NGF:

Nerve growth factor

NLS:

Nuclear localization signal

NR:

Nuclear receptor

NSCs:

Neural stem/progenitor cells

NT-3:

Neurotrophin-3

Nurr1:

Nuclear receptor-related 1 protein

PD:

Parkinson’s disease

Pex11β:

Peroxisomal membrane elongation factor

Pitx3:

Pituitary homeobox 3

PPAR:

Peroxisome-proliferator-activated receptor

PPRE:

Peroxisome-proliferator DNA response element

PRMT1:

Protein arginine methyl transferase 1

PRMT8:

Protein arginine methyl transferase 8

RA:

Retinoic acid

RAR:

Retinoic acid receptor

RARE:

Retinoic acid response element

RXR:

Retinoic X receptor

SF-1:

Steroidogenic factor 1

SGZ:

Subgranular zone

Shh:

Sonic hedgehog

SVZ:

Subventricular zone

Syp:

Synaptic vesicle protein synaptophysin

T3:

3,5,39-Triiodo-l-thyronine

T4:

3,5,39,59-Tetraiodo-l-thyronine

TH:

Tyrosine hydroxylase

TR:

Thyroid hormone receptor

TRE:

Thyroid hormone response element

VDR:

Vitamin D receptor

VDRE:

VDR response element

VMAT2:

Vesicular monoamine transporter-2

VMH:

Ventromedial hypothalamic

VMN:

Ventromedial hypothalamic nucleus

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Acknowledgements

We would like to apologize for studies that were not cited due to space limitations. We thank Daphne Antoniou, Elpinickie Ninou, Valeria Kaltezioti, Artemis Michail, and Athanasios Stergiopoulos for helpful discussions and suggestions. The authors work was supported by the Fondation Santé Grant scheme, the Greek State Scholarships Foundation (IKY) and ARISTEIA-II (NeuroNetwk, No. 4786) Grant from General Secretariat of Research and Technology (GSRT), Athens, Greece.

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  1. Dimitrios Gkikas and Matina Tsampoula contributed equally to this work.

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  1. Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, 4 Soranou Efesiou Str, 115 27, Athens, Greece

    Dimitrios Gkikas, Matina Tsampoula & Panagiotis K. Politis

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  1. Dimitrios Gkikas
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Gkikas, D., Tsampoula, M. & Politis, P.K. Nuclear receptors in neural stem/progenitor cell homeostasis. Cell. Mol. Life Sci. 74, 4097–4120 (2017). https://doi.org/10.1007/s00018-017-2571-4

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