Neem hope in brain disorder treatment

Indian scientists have shown that a compound extracted from neem seeds can reverse behavioural changes and extend the lifespan of mice genetically engineered to display features of Huntington's disease, a fatal degenerative brain disorder in humans.

By G.S. Mudur
  • Published 7.01.18
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Nihar Ranjan Jana

New Delhi: Indian scientists have shown that a compound extracted from neem seeds can reverse behavioural changes and extend the lifespan of mice genetically engineered to display features of Huntington's disease, a fatal degenerative brain disorder in humans.

The scientists at the National Brain Research Centre in Manesar, Haryana, and the Bose Institute, Calcutta, say the compound called azadiradione shows promise as a "therapeutic molecule" to delay the progression of HD, a disorder that impairs patients' abilities to think, speak and walk.

Medicine at present has no treatment to stop or reverse the progression of HD - an inherited gene-linked illness marked by the build-up of a mutant protein and the disruption of normal protein balance in brain cells.

"The molecule from neem appears to have two beneficial effects," said Nihar Ranjan Jana, a scientist at the NBRC who led the research. "It activates an enzyme that helps degrade the accumulated mutant protein and it activates a protein that helps restore normal protein balance in brain cells."

Jana and his colleagues tested the effects of azadiradione on HD model mice procured from The Jackson Laboratory, a US research centre that specialises in creating mice models for research.

The HD mice displayed muscle weakness, impaired abilities to clasp objects, an abnormal walk and molecular changes associated with HD in their brain cells. The HD mice also lost weight and lived only about 120 days, compared to their normal lifespan of two years.

Mahadeb Pal

The NBRC-Bose team found that mice injected with a 10mg per kg body weight dose of azadiradione once every two days for a month showed improved muscle strength, clasping and walking behaviour. Mice that received the injections also lived on average an extra 30 days compared to HD mice that did not receive treatment.

The findings have been accepted for publication in the journal Molecular Neurobiology.

Molecular studies on the mice brains suggest that treatment with azadiradione increased concentrations of two proteins - HSF1 and Ube3a - which, the scientists believe, may have contributed to the delay in progression of the disease in the treated mice.

Earlier studies at the NBRC and, independently, at other research centres have shown that Ube3a helps degrade mutant proteins that accumulate in HD while HSF1 helps maintain the protein quality control machinery in brain cells, thus curbing the buildup of mutant proteins.

"Azadiradione looks like a promising molecule," said Mahadeb Pal, a senior scientist at the division of molecular medicine at the Bose Institute.

Two years ago, Pal had collaborated with Subhash Mandal at Jadavpur University to establish the effects of azadiradione on HSF-1 through studies on cells and fruit-flies.

"The compound shows no toxicity at the doses we have tested," Pal said. "HSF1 is a master regulator protein - it takes corrective actions to prevent accumulation of misfolded mutant proteins in cells."

The Bose Institute scientist two years ago requested Jana to test the compound on HD mice.

The symptoms of HD - uncontrolled body movements, changes in behaviour, loss of reasoning and difficulties in speaking and swallowing - emerge between the ages of 30 and 50 years and worsen over time. Patients usually live between 15 and 20 years after diagnosis and die from pneumonia or heart failure, among other complications associated with being bed-ridden.

The Bose Institute scientists are now hoping to explore the effects of azadiradione on other degenerative brain disorders such as Alzheimer's disease and Parkinson's disease, which also involve the accumulation of mutant misfolded proteins.

The other team members are Brijesh Singh, Naman Vatsa, Vinod Nelson, Vipendra Kumar, and Shashi Kumar.