Recent Trends in Detection of Huntingtin and Preclinical Models of Huntington's Disease.

Neelima Mantha,Nandita G Das,Sudip K Das

doi:10.1155/2014/190976

Abstract

Huntington's disease is a genetically inherited neurodegenerative disease that is characterized by neuronal cell death in the brain. Molecular biology techniques to detect and quantify huntingtin protein in biological samples involve fluorescence imaging, western blotting, and PCR. Modified cell lines are widely used as models for Huntington's disease for preclinical screening of drugs to study their ability to suppress the expression of huntingtin. Although worm and fly species have been experimented on as models for Huntington's disease, the most successful animal models have been reported to be primates. This review critically analyses the molecular biology techniques for detection and quantitation of huntingtin and evaluates the various animal species for use as models for Huntington's disease.

Highlights

Huntington’s disease (HD) is a genetically inherited neurodegenerative disease that is characterized by neuronal cell death in the brain
In a HD model, if a fluorescent reporter gene is introduced in conjunction with the Htt gene, it can facilitate the detection of the Htt protein
In studies involving an in vitro model for HD in COS7 cells, Liu et al used qPCR to study the knockdown of mutant Htt gene following treatment with siRNA

Summary

Introduction

Huntington’s disease (HD) is a genetically inherited neurodegenerative disease that is characterized by neuronal cell death in the brain. The cause of HD has been identified as a mutation in the gene coding for the protein huntingtin (Htt). Htt is a ubiquitous protein occurring in both the central nervous system and peripheral tissues, with the highest levels occurring in the brain. Htt is a large protein comprising of about 3144 amino acids that has a polyglutamine (polyQ) tract in the exon-1 at the N-terminal end. Mutation in the gene leads to an increase in the number of glutamines in the polyQ tract, because of which the number of glutamines can range from 37 to 200 in affected individuals. The definite functions of the Htt protein are not clear, researchers observe that it plays important roles in transcription and cytoskeletal stability. The change in protein structure disrupts the functionality of the various transcription factors [2]

Methods for Identification and Quantitation of Htt Protein

Models of Huntington’s Disease

Symptomatic Relief of Huntington’s Disease Symptoms in Animal Models

Conclusions