Nov 16, 2019

Discovery of a potent small molecule inhibiting Huntington's disease (HD) pathogenesis via targeting CAG repeats RNA and Poly Q protein

Scientific Reports
Eshan KhanAmit Kumar


CAG repeats RNA causes various fatal neurodegenerative diseases exemplified by Huntington's disease (HD) and several spinocerebellar ataxias (SCAs). Although there are differences in the pathogenic mechanisms, these diseases share the common cause, i.e., expansion of CAG repeats. The shared cause of these diseases raises the possibility for the exploiting the common target as a potential therapeutic approach. Oligonucleotide-based therapeutics are designed earlier with the help of the base pairing rule but are not very promiscuous, considering the nonspecific stimulation of the immune system and the poor cellular delivery. Therefore, small molecules-based therapeutics are preferred for targeting the repeats expansion disorders. Here, we have used the chemical similarity search approach to discern the small molecules that selectively target toxic CAG RNA. The lead compounds showed the specificity towards AA mismatch in biophysical studies including CD, ITC, and NMR spectroscopy and thus aided to forestall the polyQ mediated pathogenicity. Furthermore, the lead compounds also explicitly alleviate the polyQ mediated toxicity in HD cell models and patient-derived cells. These findings suggest that the lead compound could act as a c...Continue Reading

  • References
  • Citations


  • We're still populating references for this paper, please check back later.
  • References
  • Citations


  • This paper may not have been cited yet.

Mentioned in this Paper

Chorionic alpha(2)-microglobulin
Nerve Degeneration
Poly(A)-Binding Proteins
Toxic Effect
Cell Growth

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

Head And Neck Squamous Cell Carcinoma

Squamous cell carcinomas account for >90% of all tumors in the head and neck region. Head and neck squamous cell carcinoma incidence has increased dramatically recently with little improvement in patient outcomes. Here is the latest research on this aggressive malignancy.

Signaling in Adult Neurogenesis

Neural stem cells play a critical role in the production of neuronal cells in neurogenesis is of great importance. Of interest is the role signalling mechanisms in adult neurogenesis. Discover the latest research on signalling in adult neurogenesis.

Psychiatric Chronotherapy

Psychiatric Chronotherapy considers the circadian rhythm as a major factor for optimizing therapeutic efficacy of psychiatric interventions. Discover the latest research on Psychiatric Chronotherapy here.

Bone Marrow Neoplasms

Bone Marrow Neoplasms are cancers that occur in the bone marrow. Discover the latest research on Bone Marrow Neoplasms here.

IGA Glomerulonephritis

IgA glomerulonephritis is a chronic form of glomerulonephritis characterized by deposits of predominantly Iimmunoglobin A in the mesangial area. Discover the latest research on IgA glomerulonephritis here.

Cryogenic Electron Microscopy

Cryogenic electron microscopy (Cryo-EM) allows the determination of biological macromolecules and their assemblies at a near-atomic resolution. Here is the latest research.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.