Elena I. Schwartz

Panacea Pharmaceuticals, Inc., Gaithersburg, MD 20877, USA

TABLE OF CONTENTS

1. Abstract

2. Introduction

3. The main steps of the mechanisms of RNA interference in mammalian cells

3.1. The siRNA pathway

3.1.1. The siRNAs effector molecules

3.1.1.1. Chemically synthesized siRNAs

3.1.1.2. RNAi vectors (RNAi inducing DNA vectors)

3.1.1.3. The post-Dicer cleavage products, siRNAs (in vitro dicing)

3.2. The miRNA pathway

4. Neurodegenerative Disease: public health challenges

5. RNAi application in neuroscience filed.

5.1. Application of RNAi in understanding mechanism of neurodegeneration in vitro

5.1.1. New delivery methods for siRNA into primary neurons

5.1.1.1. Peptide-mediated and polymer/lipid-based cellular delivery methods

5.1.1.2. The nucleofector technology

5.1.2. Mammalian RNAi libraries

5.2. RNAi in vivo technology development

5.2.1. Recent progress in the development of gene-based RNAi technology

6. RNAi therapy for neurodegenerative diseases

6.1. Overview of preclinical application of RNAi for neurodegenerative diseases

6.1.1. The first RNAi therapeutic strategy - targets a dominant disease allele.

6.1.1.1. Prion diseases

6.1.1.2. The (polyQ)-repeat disease

6.1.1.3. Huntington's disease

6.1.1.4. Spinocerebellar ataxia Type 1

6.1.2. The second RNAi therapeutic strategy - target the expression of genes involved in disease pathology

6.1.2.1. Alzheimer's disease

6.1.2.2. Parkinson's disease

6.1.2.3. Amyotrophic Lateral Sclerosis

6.2. Commercial potential of RNAi

6.3. Challenges in developing RNAi therapy for neurodegenerative diseases

7. Conclusions and perspectives

8. Acknowledgments

9. References

1. ABSTRACT