Polymorphisms,Transporter Proteins, and Targeted Therapy
Professor Randy Blakely discusses the impact of gene variation (polymorphisms) on transporter proteins. Impact can be very subtle and is linked to regulatory processes.
In the last several years, we have understood better what the impact of gene variation, or polymorphisms, can be on transporter proteins and on other genes as well. The historical concept is that gene variation can lead to many different kinds of changes in the way a gene functions. It can eliminate the gene, it can result in a gene that doesnâ€™t produce very much of the protein, it can affect certain features of the protein. I think some of that, in the last few years, weâ€™ve begun to emphasize more when we have found mutations, polymorphisms that change the ability of the biogenic amine transporter proteins to be regulated. These proteins function quite normally, but when incoming signals that would normally turn them off or turn them on in an appropriate setting arrive, these mutations prevent that from occurring. So itâ€™s a very subtle way in which mutation impacts protein function, and itâ€™s something that I think many who study genetics of neuronal proteins forget. They tend to emphasize a loss of function; theyâ€™ll say itâ€™s a defect, and when they say that, they tend to mean that the protein is gone, itâ€™s lost, it canâ€™t be replaced, or that you canâ€™t bypass it in an interesting way. But if you understand the subtlety and the way in which mutations can influence proteins, for example we found serotonin transporter mutations or polymorphisms that result in an inability to be regulated by a specific enzyme. Well, knowing that, we can turn around and say, maybe we donâ€™t need to go after the protein with a drug itself â€“ the transporter protein â€“ maybe we need to go toward the regulatory process in which itâ€™s engaged and target our therapies there.
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Doctor Randy Blakely introduces biogenic amines transporters, which remove biogenic amines such as serotonin, dopamine, and norepinephrine from extracellular space, keeping the path clear for the next pulse of neurotransmitter.
Professor Randy Blakely explains that biogenic amines include transmitters like serotonin, dopamine, and norepinephrine. Transporters assist these amines at synapses.
Doctor Randy Blakely explains that all neurotransmitters have transporters supporting their activity, which are typically involved in assisting and modulating. Genetic changes in transporters can lead to psychiatric problems.
Doctor Randy Blakely discusses the potential role of the dopamine transporter (DAT) as one element of a complex protein network in ADHD and bipolar disorder.
An interactive chromosome map of the genes and loci associated with schizophrenia.
Doctor Randy Blakely discusses the role of the dopamine and serotonin systems in a number of clinical disorders.
Doctor Randy Blakely describes an intriguing hypothesis for why amphetamine may be effective in treating some individuals with ADHD.
Doctor Randy Blakely speculates that the traditional view that drugs though to increase serotonin and dopamine levels in the brain may work by preventing a backward-running state.
Doctor Randy Blakely discusses the association between the dopamine transporter and ADHD, and discusses a possible relationship with bipolar disorder and schizophrenia.
Mark Skolnick talks about using RFLPs or SNPs to study patterns in families