Inge Heulens¹, Frank Kooy¹

1Department of Medical Genetics, University of Antwerp, Antwerp, Belgium

TABLE OF CONTENTS

1. Abstract

2. Introduction

3. Structure and function of FMRP

4. Animal models to study the fragile X syndrome

4.1. Mouse models (Mus Musculus)

4.1.1. Fragile X mouse

4.1.2. Rescue mouse

4.1.3. CGG repeat mouse

4.1.4. I304N mouse

4.2. Fly models (Drosophila melanogaster)

4.3. Zebrafish models (Danio rerio)

5. Major molecular pathways involved in the fragile X syndrome

5.1. The GABAergic pathway

5.2. mGluR related pathways

5.2.1. The mGluR theory

5.2.2. The ERK pathway

5.2.3. Glycogen synthase kinase

5.3. The Rho GTPase pathway

5.4. The neuroendocrine system

5.4.1. The hypothalamic-pituitary-adrenal axis

5.4.2. Melatonin homeostasis

5.4.3. Other hormones in the neuroendocrine system

5.5. The cholinergic system

6. Treatments in the fragile X syndrome

6.1. Non-pharmacological interventions

6.2. Symptom-based pharmacological treatment

6.3. Targeted pharmacological treatment

6.3.1. Drugs interacting with the GABAA receptor

6.3.2. Drugs interacting with the mGluR pathway

6.3.2.1. MPEP

6.3.2.2. Fenobam

6.3.2.3. STX107

6.3.2.4. CX516

6.3.2.5. Lithium

6.3.3. Arbaclofen (STX209)

6.3.4. Drugs interacting with the neuroendocrine system

6.3.4.1. Mifepristone

6.3.4.2. Melatonin

6.3.5. Donepezil

6.3.6. Minocycline

6.4. Additional clinical trials

7. Perspectives

8. Acknowledgement

9. References

1. ABSTRACT