The therapeutic potential of siRNA in gene therapy of neurodegenerative disorders

J Neural Transm Suppl. 2007:(72):43-9. doi: 10.1007/978-3-211-73574-9_7.


RNA interference using small inhibitory RNA (siRNA) has become a powerful tool to downregulate mRNA levels by cellular nucleases that become activated when a sequence homology between the siRNA and a respective mRNA molecule is detected. Therefore siRNA can be used to silence genes involved in the pathogenesis of various diseases associated with a known genetic background. As for many neurodegenerative disorders a causative therapy is unavailable, siRNA holds a promising option for the development of novel therapeutic strategies. Here we discuss different siRNA target strategies aiming for an allele-specific degradation of disease-inducing mRNA and we review the literature in the field of siRNA and its application in animal models of neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and spinocerebellar ataxia (SCA1).

Publication types

  • Review

MeSH terms

  • Alleles
  • Alzheimer Disease / genetics
  • Alzheimer Disease / therapy
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Disease Models, Animal
  • Down-Regulation / genetics
  • Gene Expression / physiology
  • Gene Silencing*
  • Gene Transfer Techniques*
  • Genetic Therapy / methods*
  • Humans
  • Huntington Disease / genetics
  • Huntington Disease / therapy
  • Motor Neuron Disease / genetics
  • Motor Neuron Disease / therapy
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / therapy
  • Point Mutation
  • Protease Nexins
  • RNA, Messenger / genetics*
  • RNA, Small Interfering*
  • Receptors, Cell Surface / genetics
  • Sequence Analysis, DNA
  • Spinocerebellar Ataxias / genetics
  • Spinocerebellar Ataxias / therapy


  • Amyloid beta-Protein Precursor
  • Protease Nexins
  • RNA, Messenger
  • RNA, Small Interfering
  • Receptors, Cell Surface