Quality Control in Huntington’s Disease: a Therapeutic Target.

Quality Control in Huntington’s Disease: a Therapeutic Target.

Publication date: Jul 11, 2019

Huntington’s disease (HD) is a fatal autosomal dominantly inherited brain disease caused by excessively expanded CAG repeats in gene which encodes huntingtin protein. These abnormally encoded huntingtin proteins and their truncated fragments result in disruption of cellular quality mechanism ultimately triggering neuronal death. Despite great efforts, a potential causative agent leading to genetic mutation in HTT, manifesting the neurons more prone to oxidative stress, cellular inflammation, energy depletion and apoptotic death, has not been established yet. Current scenario concentrates on symptomatic pathologies to improvise the disease progression and to better the survival. Most of the therapeutic developments have been converged to rescue the protein homeostasis. In HD, abnormal expansion of glutamine repeats in the protein huntingtin leads to toxic aggregation of huntingtin which in turn impairs the quality control mechanism of cells through damaging the machineries involved in removal of aggregated abnormal protein. Therapeutic approaches to improve the efficiency of aggregate clearance through quality control mechanisms involve protein folding machineries such as chaperones and protein degradation machineries such as proteasome and autophagy. Also, to reduce protein aggregation by enhancing proper folding, to degrade and eliminate the aggregates are suggested to negatively regulate the HD progression associated with the disruption of protein homeostasis. This review focuses on the collection of therapeutic strategies targeting enhancement of protein quality control activity to delay the HD pathogenesis.

Rai, S.N., Singh, B.K., Rathore, A.S., Zahra, W., Keswani, C., Birla, H., Singh, S.S., Dilnashin, H., and Singh, S.P. Quality Control in Huntington’s Disease: a Therapeutic Target. 06572. 2019 Neurotox Res.

Concepts Keywords
Apoptotic Branches of biology
Autophagy Huntington’s disease
Autosomal Huntingtin
Brain Organelles
Causative Protein complexes
Chaperones Proteins
Energy Proteasome
Genetic Mutation Autophagy
Glutamine Trinucleotide repeat disorder
Homeostasis Aggresome
Huntingtin Protein
Oxidative Stress


Type Source Name
pathway BSID Proteasome
pathway BSID Protein folding
drug DRUGBANK L-Glutamine
drug DRUGBANK Tropicamide
disease MESH disease progression
disease MESH inflammation
pathway BSID Oxidative Stress
disease MESH oxidative stress
disease MESH death
disease DOID brain disease
disease MESH brain disease


Original Article

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