In-silico analysis for RNA-interference mechanism of α-synuclein to treat Parkinson's disease

Int J Bioinform Res Appl. 2013;9(6):557-75. doi: 10.1504/IJBRA.2013.056630.

Abstract

Parkinson's Disease (PD) causing mutations in α-synuclein gene are ALA30PRO, GLU46LYS and ALA53THR. The conformational changes in proteins with respect to all the three mutations were analysed. These were used to predict the structures of Short Interfering RNA (siRNA) antisense strand and siRNA region. The siRNA binds with the argonaute protein forming RNA Induced Silencing Complex (RISC). Then, siRNA antisense-strand was attached to RISC. The structure of dicer (RNase-III-enzyme) cleaves double-stranded RNA (dsRNA) into two siRNA-strands. Incorporation of single siRNA-strand into RISC guides to pair with the complementary α-synuclein target-messenger RNA (mRNA) thereby enabling it to cleave the target.

Keywords: PD; Parkinson' RNA biotools; RNA interference; alpha–synuclein; antisense RNA; bioinformatics; gene silencing; molecular neuroscience; molecular structure; protein conformational changes; proteins; s disease; short interfering RNA; siRNA; structural biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism
  • Computer Simulation
  • Humans
  • Parkinson Disease / genetics*
  • Parkinson Disease / therapy*
  • Protein Conformation
  • RNA Interference*
  • RNA, Double-Stranded / metabolism
  • RNA-Induced Silencing Complex / genetics
  • RNA-Induced Silencing Complex / metabolism
  • alpha-Synuclein / genetics*
  • alpha-Synuclein / metabolism

Substances

  • Argonaute Proteins
  • RNA, Double-Stranded
  • RNA-Induced Silencing Complex
  • alpha-Synuclein