The medical community is now a step closer to having a drug that can cure dementia and memory loss. A research team from the Korea Institute of Science and Technology (KIST) and KAIST have discovered that reactive astrocytes, which have been commonly observed in Alzheimer’s patients, aberrantly and abundantly produce the chief inhibitory neurotransmitter GABA and release it through the Best1 channel. The released GABA strongly inhibits neighbouring neurons to cause impairment in synaptic transmission, plasticity and memory. This discovery will open a new chapter in the development of new drugs for treating such diseases.
Alzheimer’s disease, which is the most common cause of dementia, is fatal and currently, there is no cure. In Alzheimer’s disease, brain cells are damaged and destroyed, leading to devastating memory loss. It is reported that 1 in 8 Americans aged 65 or over have Alzheimer’s disease. In 2011, 7,600 elderly people with dementia lost their way back home and became homeless in Korea. However, to date, there has been no clear understanding of the mechanisms underlying dementia in Alzheimer’s disease. So far, neuronal death is the only proposed mechanism available in scientific literature.
The research team discovered that reactive astrocytes in the brains of a mouse-based Alzheimer’s disease model produce the inhibitory transmitter GABA by way of the enzyme Monoamine oxidase B (MAO-B) and release GABA through the Bestrophin-1 channel to suppress normal information flow during synaptic transmission. Based on this discovery, the team was able to reduce the production and release of GABA by inhibiting MAO-B or Bestrophin-1, and successfully ameliorate impairments in neuronal firing, synaptic transmission and memory in Alzheimer’s disease model mice.
In behavioural tests, the team used the fact that mice tend to prefer dark places. If a mouse experiences an electric shock in a dark place, it will remember this event and avoid dark places from then on. However, the mouse with modelled Alzheimer’s disease did not remember the associated shock and returned to the dark places. The team demonstrated that treating these mice with a MAO-B inhibitor fully recovered the memory of the study’s mice. The selegiline is currently used in Parkinson’s disease as an adjunct therapy and considered as a one of best promising medicine for MAO-B inhibitor. But it has been previously shown to be less effective in Alzheimer’s disease.
The team proved that selegiline is effective for a short time, but when it is used in long term, it loses its efficacy in Alzheimer’s disease modelled mice. When treated for 1 week, selegiline brought the neuronal firing to a normal level. But when it was treated for 2 and 4 weeks, neuronal firing came back to the levels of untreated mice. From these results, the team proposed that there is a pressing need for a new drug that has long lasting effects.
This study has revealed the novel mechanism of how Alzheimer’s patients might lose their memory. The team have also proposed new therapeutic targets, which include GABA production and release mechanisms in reactive astrocytes for treatment of Alzheimer’s disease. Furthermore, the team have provided a stepping stone for the development of MAO-B inhibitors with long lasting efficacy.
Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.
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Michelle Petersen’s copy was used in the highly successful marketing campaign for the mega-hit film ‘Jumanji: The Next Level, starring Jack Black, Karen Gilian, Kevin Hart and Dwayne ‘The Rock’ Johnson. Michelle Petersen’s copywriting was part of the film’s coverage by the Republic TV network. Republic TV is the most-watched English language TV channel in India since its inception in 2017.
An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.