Inhibiting Fatty Acid Enzyme Protects Mice with Alzheimer's
Related study shows that cell transplant relieves amyotrophic lateral sclerosis
MONDAY, Oct. 20 (HealthDay News) -- Inhibiting an enzyme involved in fatty acid production can protect against the harmful consequences of Alzheimer's disease in mice, according to study findings published online Oct. 19 in Nature Neuroscience. A related paper published in the same journal on the same day shows that transplanting astrocyte precursors into the motor neurons of a mouse model of amyotrophic lateral sclerosis (ALS) can alleviate some of the poor outcomes of the disease.
In the first study, Rene O. Sanchez-Mejia, M.D., from the University of California San Francisco, and colleagues profiled the fatty acids present in the brain tissues of mice producing the mutant human amyloid precursor protein present in patients with familial Azheimer's disease. They found increased levels of arachidonic acid and its metabolites, which are produced by the group IV isoform of phospholipase A2 (GIVA-PLA2). Inhibiting the enzyme reduced the toxicity of amyloid-beta peptides and could protect the mice against deficits in learning and memory, behavioral alterations, and premature mortality.
In the second study, Angelo C. Lepore, from Johns Hopkins University School of Medicine in Baltimore, and colleagues transplanted lineage-restricted astrocyte precursors around cervical spinal cord respiratory motor neuron pools in mice producing mutant human superoxide dismutase 1 protein, a model of ALS. They found that the cells were neuroprotective, extending survival and disease duration, reducing motor neuron loss, and delaying declines in motor and respiratory function. The effect was partly dependent on an astrocyte glutamate transporter.
"These findings indicate the feasibility and efficacy of transplantation-based astrocyte replacement and show that targeted multisegmental cell delivery to the cervical spinal cord is a promising therapeutic strategy for slowing focal motor neuron loss associated with ALS," Lepore and colleagues conclude.