High throughput screening for neurodegeneration and complex disease phenotypes

Comb Chem High Throughput Screen. 2008 Mar;11(3):238-48. doi: 10.2174/138620708783877753.


High throughput screening (HTS) for complex diseases is challenging. This stems from the fact that complex phenotypes are difficult to adapt to rapid, high throughput assays. We describe the recent development of high throughput and high-content screens (HCS) for neurodegenerative diseases, with a focus on inherited neurodegenerative disorders, such as Huntington's disease. We describe, among others, HTS assays based on protein aggregation, neuronal death, caspase activation and mutant protein clearance. Furthermore, we describe high-content screens that are being used to prioritize hits identified in such HTS assays. These assays and screening approaches should accelerate drug discovery for neurodegenerative disorders and guide the development of screening approaches for other complex disease phenotypes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Drug Evaluation, Preclinical / methods*
  • Humans
  • Huntington Disease / drug therapy
  • Huntington Disease / metabolism
  • Nerve Tissue Proteins / analysis
  • Nerve Tissue Proteins / metabolism
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / metabolism
  • Protein Binding / drug effects
  • Small Molecule Libraries / pharmacology


  • Nerve Tissue Proteins
  • Small Molecule Libraries