The protein FKBP12 regulates several important cell signaling pathways, and decreasing its activity enhances long-term potentiation in the hippocampus, said Dr. Susan Hamilton, chair of molecular physiology and biophysics at BCM and a senior author of the report. (Long-term potentiation means the enhancement of the synapse or communication between neurons.)

It accomplishes this by fine-tuning a particular pathway called mTOR signaling (mammalian target of rapamycin). The mice in whose brains the activity of the gene was reduced had longer memories and were more likely to exhibit repetitive behaviors than normal mice.

"These studies may offer insight into the molecular underpinnings of repetitive behaviors such as those seen in autism spectrum disorder, obsessive compulsive disorder, schizophrenia and other neurodegenerative disorders," said Hamilton. "Because these studies involved interrupting the mTOR signaling after birth, they challenge the idea that some aspects of these conditions are developmentally predetermined."

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However, a new research study led by Dr. David A. Fidock from Columbia University showed that disruption of the FabI gene in P. falciparum or the rodent parasite P. berghei did not impede blood stage growth and that FabI was not the antimalarial target of triclosan. Fidock and colleagues also showed that triclosan was not as effective against the blood stage of the malaria parasite as was previously thought. "Although this enzyme has been extensively studied as a candidate drug target for blood stage malaria parasites, our data argue against the therapeutic potential of FabI, and indeed the entire FAS-II pathway, during infection of red blood cells," explains Dr. Fidock.

Nevertheless, Dr. Fidock and his colleagues went on to make an additional discovery. They demonstrated that an absence of FabI results in P. berghei parasites that, coming from the mosquito, are less infective and fail to complete the liver stage of development. These parasites are then typically unable to initiate the symptomatic blood stage infection. In contrast, during the blood stage, the parasites do not rely on FabI and appear to obtain fatty acids primarily by acquiring them from the host.

"We propose that therapeutic strategies to interfere with fatty acid processes in blood stage parasites should focus on scavenging these molecules taken from the host. This contrasts with liver stage parasites that depend on synthesizing their own fatty acids to meet their metabolic needs. Interference with FAS-II in liver stages now offers novel perspectives for prophylactic intervention," explains Dr. Fidock. "Our work also highlights the need for additional studies to elucidate how triclosan acts on blood stage parasites."

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