Fibril-induced neurodegenerative disorders in an Aβ-mutant Drosophila model: therapeutic targeting using ammonium

Sudipa Manna1, Puja Karmakar, Bikash Kisan

  • 1Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India. bkac@barc.gov.in jyotim@barc.gov.in.

Chemical Communications (Cambridge, England)
|August 5, 2021
PubMed

Insights

Polyanionic molybdate effectively breaks down harmful protein fibrils in lab tests and in a fly model of neurodegenerative disease. Ammonium molybdate shows therapeutic potential for Alzheimer

Area of Science:

  • Biochemistry
  • Neuroscience
  • Biotechnology

Background:

  • Protein misfolding and fibril formation are hallmarks of neurodegenerative diseases like Alzheimer's.
  • Developing effective inhibitors and degraders of these toxic protein aggregates is a critical therapeutic challenge.

Purpose of the Study:

  • To investigate the efficacy of polyanionic molybdate in inhibiting and degrading protein fibrils.
  • To evaluate the therapeutic potential of ammonium molybdate in a relevant in vivo model of Alzheimer's disease.

Main Methods:

  • In vitro studies using insulin protein fibrils.
  • In vivo experiments utilizing a Drosophila fly model expressing Aβ42 mutations.

Main Results:

  • Polyanionic molybdate demonstrated the ability to inhibit and degrade protein fibrils in vitro.
  • Molybdate treatment led to the disappearance of fibrillar structures in Drosophila flies.
  • Aβ42-mutant flies treated with molybdate showed recovery from neurodegenerative symptoms compared to controls.

Conclusions:

  • Polyanionic molybdate effectively targets and eliminates pathogenic protein aggregates.
  • Ammonium molybdate exhibits significant therapeutic potential for Alzheimer's disease treatment.