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In a recent study published by Nature Medicine, researchers investigated the genetic predispositions to developing dementia.
A common form of inherited early-onset dementia that occurs within the frontal and temporal lobes of the brain is often caused by tau, granulin precursor (GRN), and chromosome 9 open reading frame 72 (C9orf72) gene mutations. However, it has yet to be fully elucidated how these genes precisely cause the loss of neuronal function and brain cell death. In a study published in Nature Medicine, Swarup and colleagues utilized mouse models to discern the exact genetic processes involved in neurodegeneration.
As opposed to using only one inbred mouse strain, Swarup and colleagues thought that investigating three genetically distinct strains of mice would lead to broader implications for their work. To identify the exact genetic processes involved in frontotemporal dementia, the researchers observed the genetic activity within different areas of the degenerating mouse brain at various time points.
They found two gene clusters that cause an overproduction of tau – a common trademark observed in neurodegenerative disease such as dementia that induces brain cell death. More specifically, the researchers pinpointed a microRNA module called miR-203 that regulates the neurodegeneration.
Thereafter, Swarup and colleagues searched through a database of experimental drugs and their effects upon genetic mutations to identify any potential therapeutic approaches. When these drugs were tested on human cell cultures, dementia-induced neurodegeneration ceased.
As there is no current treatment that can effectively halt the progression of dementia, the work of Swarup and colleagues is pivotal to neurodegenerative disease research. Pharmaceutical companies commonly target beta-amyloid in their products; however, the study suggests that directing their efforts to tau may combat dementia by preventing deterioration of the brain. Although the work is still within its infancy, senior author of the study Daniel Geschwind nevertheless denotes that “[…] this is an encouraging step”.
Written by Helen Marzec
- Swarup, V., Hinz, F., Rexach, J., Noguchi, K., Toyoshiba, H., & Oda, A. et al. (2018). Identification of evolutionarily conserved gene networks mediating neurodegenerative dementia. Nature Medicine. doi: 10.1038/s41591-018-0223-3
- Gordon, D. UCLA researchers discover genes tied to dementia in key early step toward new therapies. (2018). Retrieved from http://newsroom.ucla.edu/releases/ucla-gene-link-dementia-key-step-toward-new-therapies