Saving synapses in Alzheimer’s disease- thrombospondin to the rescue!

Lay summary by Kristyn Bates

Alzheimer’s disease (AD) is a devastating neurodegenerative disease, affecting approximately 44 million people worldwide. AD is characterised by deterioration in learning and memory abilities and significant neuronal loss, brain inflammation and destruction of neuronal communication networks, termed synapses. Synaptic loss correlates well with disturbances in brain function and therefore preventing synaptic loss and dysfunction and saving cells before they die is an attractive target for treating AD.

Synaptic function doesn’t just rely on neurons though. Astrocytes are a type of glial cell in the central nervous system, and are important regulators of brain function, including the formation and modulation of synapses. Astrocytes release large proteins called thrombospondins that regulate the formation of new synapses, new neuronal connections, in the brain.

Thrombospondins form the basis of new research published by Dr Mook-Jung and colleagues from the Seoul National University College of Medicine. In a series of experiments conducted in animal and cell culture models of AD, along with tissue from AD patients, Dr Mook-Jung’s team has provided evidence suggesting that thrombospondins could be a key target in the fight against AD.

The team first established that brains affected by AD have much lower levels of thrombospondins and other synaptic proteins than control brains in both human and animal AD models. They next showed that release of thrombospondins decreased when astrocytes were exposed to amyloid-beta (Aβ). Aβ is a key protein involved in AD pathology because it attacks and destroys synapses. The authors demonstrated that treating neuronal cells with thrombospondins prevented synaptic loss triggered by exposure to Aβ. Thrombospondins also restored synaptic function in cells that had been exposed to Aβ, suggesting a dual-protective role against Aβ-induced synaptic dysfunction and loss. The team also identified the neuronal receptor responsible for the protective effect of thrombospondins, which is an important advance in the design of new drugs to specifically target certain cellular elements.

Lastly, the team investigated whether thrombospondins could be used as a possible drug to treat AD symptoms. They injected thrombospondin protein directly into the brains of AD-mice that have been genetically modified to over-produce Aβ in the brain. Thrombospondin-treatment increased levels of synaptic proteins, suggesting that thrombospondin treatment could help maintain synapses and protect them against Aβ toxicity.

AD is estimated to cost approximately $605 billion per annum globally, which is equivalent to 1% of the world’s gross domestic product. New therapies are desperately needed and finding ways to protect neurons and maintain function before cell loss is particularly important. The current study shows that saving synapses via thrombospondin signalling pathways may prove useful in the protecting the brain against AD.

For further information

Read the Neurobiology of Aging original research article which this summary is based on Thrombospondin-1 prevents amyloid beta–mediated synaptic pathology in Alzheimer’s disease (September 2015).

Visit the profile of the research ambassador, Kristyn Bates, who wrote this summary.

STM Digest is a collection of lay summaries published next to original research articles on ScienceDirect, provided free of charge, and accessible to everyone.

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