Potential Anticancer Drug Could Serve as Novel Alzheimer’s Disease Treatment

Potential Anticancer Drug Could Serve as Novel Alzheimer’s Disease Treatment

A drug developed as a potential anticancer agent could serve as a new treatment for Alzheimer’s disease. The drug targets an enzyme in order to disrupt cancerous growth, but researchers at the University of Alabama at Birmingham (UAB) School of Medicine have demonstrated that the drug also helps to protect nerve cell dendritic spines. The loss of those spines is associated with cognitive decline in Alzheimer’s patients.

Alzheimer’s disease is characterized by β-amyloid deposits that form into plaques along with the development of neurofibrillary (tau) tangles in the brain. A previous study suggested cognitive decline is more closely associated with synaptic loss and dendritic spine damage than the presence of the plaques themselves.

In the study Jeremy Herskowitz, PhD, assistant professor in the department of neurology, School of Medicine at UAB, and his team showed that individuals with long dendritic spines did not develop dementia, even if they had the signs of Alzheimer’s Disease – Plaques and tau tangles.

The research suggested an enzyme called LIMK1 was regulating dendritic spine size and density and that activity was upregulated in patients with Alzheimer’s disease. With the enzyme upregulated, dendritic spine damage occurs.

Currently, there are no therapeutic strategies that target the loss of synapses and dendritic spines, but the drug developed as an anticancer agent – SR7826 – could be the first. The latest research suggests it could be used to slow or even prevent cognitive impairment by protecting the dendritic spines.

In experiments on mice, the researchers demonstrated inhibiting serine/threonine kinase LIMK1 with SR7826 had a protective effect which Herskowitz called “significant and promising” with no observed side effects. In experiments on cultured rat neurons in a mouse model of AD, after ten days of daily treatment with SR7826 dendritic spine density and length increased.

Previous attempts have been made to inhibit synaptic loss by targeting Rho-associated kinases (ROCKs) which are upstream of LIMK1. Compounds developed to target ROCKs have been found to have severe side effects and have not made it to clinical trials. The latest study suggests that while ROCKs play a role in dendritic spine density and length, they do so via a different pathway. The researchers hope the side effects of blocking ROCK activity will be avoided.

“This is one of the first scientific papers to suggest that LIMK1 might be a better target for intervention than the ROCK kinases,” said Herskowitz. Another important aspect of this sort of target is that it could lead to an intervention before loss of cognitive function has begun. It could provide a protective effect to prevent damage or loss of dendritic spines.”

Further information can be found in the paper – Pharmacologic inhibition of LIMK1 provides dendritic spine resilience against β-amyloid – which was recently published in the journal Science Signalling. DOI: 10.1126/scisignal.aaw9318

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