Exclusive Interview: Tufts Research Team On Protein Link To Autism

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Recently, ICare4Autism had the pleasure of interviewing Dr. Michele H. Jacob, a Neuroscience Professor at Tufts University School of Medicine, and PhD candidate Jesse Mohn from the Sackler School of Graduate Biomedical Sciences at Tufts. Both Dr. Jacob and Mr. Mohn have been doing testing on a protein called APC (adenomatous polyposis coli), which they believe plays a key role in synapse maturation and displays an important link to autism. We spoke in length about the connection of APC with autism and what the results of their study could potentially uncover about ASD.

Q: To begin, your research links the protein APC with autism. APC is said to play a key role in synapses maturation, and is therefore important in the transmission of neural messages in the body. For those of our readers who may not have a thorough understanding of APC, can you provide us with some insight on what exactly it is and how it is related to autism?

MHJ: Basically, this is a protein that is in every cell of the body and it has multiple functions. These functions depend on the fact that it has different protein binding partners. The functions of APC are different across the diverse cell types and through the distinct stages of development. The key to autism comes from the observation in the medical literature that patients who have mutations in the gene that encodes this protein tend to have cognitive deficits, varied cases of mental retardation and autism. We gathered that APC was potentially playing a role in the brain and we got very interested in what the role of APC would be in nerve cells and synapses. Our data supports the idea that APC is a critical player and it directs that maturation of the synapses. In the paper we just published, we also found that it’s really important for localizing neuroligin and neurexin synapses and those proteins have both been implicated in autism

Q: Mutations in the genes for neuroligin and neurexin are associated with autism in humans- to what degree does mutation occur in individuals with autism?

MHJ: There have been a lot of studies looking at the changes in genes in patients with autism compared to sibling controls for example, and mutations in neuroligin and neurexin, which encode a family of gene clouds. There have been a strong correlations in the literature for neuroligin 1, 3, and 4 and neurexin all being implicated as genetic variants that have been seen in people with autism.

Q: Could the lack of APC in individuals with autism be corrected? If so, is it possible that their symptoms would reduce?

MHJ: One of the things we are hoping to do in our future studies is nail down which particular functions of APC are involved in the phenotype (for example: the autistic like behavior). There are different interactions in APC that could be modified by different manipulations, even potentially drugs that are used today. And so we are hoping that ultimately we would gain insight into potential treatments for some of the symptoms caused by APC mutations and hopefully that would include the autistic symptoms.

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Q: How feasible is it to manipulate APC?

MHJ: It depends on which of its multiple functions we are talking about. Some functions of APC can be manipulated by drug treatment and others might require more of a genetic manipulation and that’s the type of thing we want to pursue; to figure out what we can do and what approaches are reasonable.

Q: What could the results of this study mean for the neuroscience community and those affected by autism?

MHJ: We would very much love to be able to develop insights; the goal of our work is to start to understand in molecular terms, what are the changes that are causing these behaviors in people.  And I think that tying these things together, and showing the connection between neuroxin, neuroligin and APC and knowing that mutations in all three are associated with autism is giving us further insight as to what could be going on in the brains of people who have these changes in their behavior. And so, I think the more people focus on this and the more people understand these relationships, we will be able to develop approaches to prevent these changes.

Q: What are the next steps for your lab? Are you planning on conducting follow up research?

JM: We are now moving to a mouse model. In this model, we basically removed APC from being expressed in neurons in the brain and characterized the changes in these mice. We have seen that when APC is missing, we see changes in behavior that are consistent and mimic autistic behavior. These changes include: lower social interaction and impairments in learning and memory.

MHJ: We are hoping with the mouse model, and the manipulation of APC we can see which of the APC functions cause the different phenotypes. Ultimately, we can use this as a way to reverse the deficits we are finding.

– – – – – – INTERVIEW CONCLUDES- – – – – –

Still, want more info on this? The findings of this study were published in the August 18 issue of The Journal of Neuroscience. To read more about this research, you can visit the Sackler School of Graduate Biomedical Sciences at Tufts by clicking here.

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