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Novel treatments for neurodegenerative disorders

Developing treatments that stop underlying damage in neurodegenerative disorders

Developing treatments that stop underlying damage in neurodegenerative disorders

Regeneration in the nervous system is slow compared with other body systems. Picture: Science Photo Library

Neurogenerative diseases manifest in an abnormal build-up of proteins in the brain. This often involves misfolded proteins such as the tangles of the protein tau found in Alzheimer’s disease and the abnormal cluster of proteins that form the Lewy bodies associated with Parkinson’s disease. These changes can lead to inflammation, synaptic insufficiency and cell death.

Treatments focus only on symptom relief without altering disease progression. Patients with Alzheimer’s disease may be treated with medication such as donepezil which increases levels of the neurotransmitter, acetylcholine. This improves the function of remaining cells, but does not slow the build up of abnormal proteins or the rate of cell death.

In Parkinson’s disease, the reduced levels of dopamine in the brain can be increased by giving drugs such as carbidopa levodopa, but the damage process continues and the effectiveness of the drug declines with prolonged use.

Understanding what goes wrong could help in developing treatments that stop the underlying damage. The proper folding of proteins is usually controlled by a quality system that includes molecular chaperones which can rearrange misfolded proteins. Despite this system, many proteins fail to fold normally because of multiple factors like ageing, oxidative stress, gene mutations and altered cellular temperature.

One line of research is to manipulate heat shock proteins, a family of proteins that are produced by cells in response to exposure to stressful conditions. Different types of these proteins have different actions, so it may be possible in the future to use specific heat shock proteins to stop the damage to the brain seen in neurological diseases.

Hussain R, Zubair H, Pursell S et al (2018) Neurodegenerative diseases: regenerative mechanisms and novel therapeutic approaches. Brain Sciences. 8, 9, 177.

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