Home Cellular science Brain tissue mechanism may explain why women are more susceptible to Alzheimer’s disease

Brain tissue mechanism may explain why women are more susceptible to Alzheimer’s disease

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Researchers have found that women naturally express higher levels of an X-linked enzyme called ubiquitin-specific peptidase 11 (USP11). Higher levels of USP11 lead to greater buildup of a protein called tau, which is responsible for forming clumps of toxic proteins inside the brain nerve cells of patients with Alzheimer’s disease.


The presence of a chemical tag called ubiquitin on tau is regulated by a balanced system of enzymes that add or remove the ubiquitin tag. The body normally destroys unnecessary tau. But when overabundant levels of USP11 disrupt this process, tau can pathologically aggregate, causing nerve cell destruction and tau pathologies, or taupathies, including Alzheimer’s disease.


The researchers also found that when they genetically knocked out USP11 in a mouse model, females were preferentially protected from tauropathy. Their results suggest that excessive activity of the USP11 enzyme in women leads to their increased susceptibility to Alzheimer’s disease.


“We are particularly excited about this finding as it provides a foundation for the development of new neuroprotective drugs,” co-lead author David Kang, PhD, professor of pathology at Case Western, said in a statement. “The good news is that USP11 is an enzyme, and enzymes can traditionally be pharmacologically inhibited. Our hope is to develop a drug that works in this way, to protect women from the higher risk of developing the disease. Alzheimer’s.”


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