Zebrafish an experimental model of Huntington's disease: molecular aspects, therapeutic targets and current challenges

Mol Biol Rep. 2021 Dec;48(12):8181-8194. doi: 10.1007/s11033-021-06787-y. Epub 2021 Oct 19.

Abstract

Huntington disease (HD) is a lethal autosomal dominant neurodegenerative disease whose exact causative mechanism is still unknown. It can transform from one generation to another generation. The CAG triplet expansion on polyglutamine (PolyQ) tract on Huntingtin protein primarily contributes in HD pathogenesis. Apart from this some another molecular mechanisms are also involved in HD pathology such as loss of Brain derived neurotrophic factor in medium spiny neurons, mitochondrial dysfunction, and alterations in synaptic plasticity are briefly discussed in this review. However, several chemicals (3-nitropropionic acid, and Quinolinic acid) and genetic (mHTT-ΔN17-97Q over expression) experimental models are used to explore the exact pathogenic mechanism and finding of new drug targets for the development of novel therapeutic approaches. The zebrafish (Danio rerio) is widely used in in-vivo screening of several central nervous system (CNS) diseases such as HD, Alzheimer's disease (AD), Parkinson's disease (PD), and in memory deficits. Thus, this makes zebrafish as an excellent animal model for the development of new therapeutic strategies against various CNS disorders. We had reviewed several publications utilizing zebrafish and rodents to explore the disease pathology. Studies suggested that zebrafish genes and their human homologues have conserved functions. Zebrafish advantages and their characteristics over the other experimental animals make it an excellent tool for the disease study. This review explains the possible pathogenic mechanism of HD and also discusses about possible treatment therapies, apart from this we also discussed about possible potential therapeutic targets which will helps in designing of novel therapeutic approaches to overcome the disease progression. Diagrammatic depiction shows prevention of HD pathogenesis through attenuation of various biochemical alterations.

Keywords: HD mechanisms; Huntington disease; Neurodegeneration; Therapeutic approaches; Therapeutic targets; Zebrafish.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / metabolism
  • Disease Models, Animal*
  • Humans
  • Huntingtin Protein / genetics
  • Huntingtin Protein / metabolism
  • Huntington Disease / genetics
  • Huntington Disease / metabolism*
  • Huntington Disease / pathology*
  • Neurodegenerative Diseases / metabolism
  • Neuronal Plasticity / physiology
  • Neurons / metabolism
  • Zebrafish / metabolism
  • Zebrafish Proteins / metabolism

Substances

  • Huntingtin Protein
  • Zebrafish Proteins