New insight into Neurodegenerative Diseases

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The prevention and treatment of neurodegenerative diseases is particularly complex. Devising strategies to reduce this degeneration depend on the disease and the individual affected. Unfortunately, most treatments have, so far, been poor or unsuccessful.

Therefore, in order to understand and reflect on these diseases and develop effective treatments, comprehensive research and classification of the proteins responsible for this degeneration becomes highly significant.

Tau is a protein that stabilises neuronal microtubules. On the downside, however, tau may undergo modifications resulting in the generation of aberrant aggregates which are toxic to neurons. Tau is known to build up in over 20 neurodegenerative diseases, such as Alzheimer’s disease, damaging brain cells that are essential for learning and memory.

Source: P. Serrano Castro, news-medical.net.

The abnormal build-up of Tau is caused by increased activity of enzymes (Tau kinases), causing the Tau protein to misfold and clump, forming tangles. Tau protein can be detected using PET scans of the brain and lab tests of spinal fluid.

Source: Imaging of Tau proteins, Karolinska Institutet. Chiotis, et al.

Interestingly, a new study has successfully reversed the harmful effects of Tau. The researchers found a protein which Tau interacts with in the brain, called Synaptogyrin-3. Tau binds to Synaptogyrin-3 on synaptic vesicles. The researchers managed to successfully knockout (remove) Synaptogyrin-3 in mice, and they found that they could prevent the loss of synapses caused by the Tau protein! In turn, this reversed the working memory decline that had been seen in the mice and restored synaptic plasticity (allowing neuron growth and reorganization).

Curiously, this was successfully done without reducing inflammation in the brain, indicating that Tau triggers neuroinflammation and synaptic loss separately. This also means that the destruction of synapses, independent from neuroinflammation, is a leading cause for cognitive decline. The researchers plan to now develop drugs that would lower the levels of Synaptogyrin-3 in the brain, to investigate whether this would work as a treatment for Alzheimer’s disease and other neurodegenerative conditions!

Relevant sources:

Original Study:
Pablo Largo-Barrientos, Nuno Apóstolo, Eline Creemers, Zsuzsanna Callaerts-Vegh, Jef Swerts, Caitlin Davies, Joseph McInnes, Keimpe Wierda, Bart De Strooper, Tara Spires-Jones, Joris de Wit, Valerie Uytterhoeven and Patrik Verstreken (2021). Lowering Synaptogyrin-3 expression rescues Tau-induced memory defects and synaptic loss in the presence of microglial activation. Neuron.

Accessible at: https://www.cell.com/neuron/fulltext/S0896-6273(20)30998-3

Featured photo source:
Excalibur Healthcare, NJ. 2021.

Edited by Malavika Ramanand

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