Scientists discover brain cell development process implicated in mental retardation

Scientists at Rutgers, The State University of New Jersey, have discovered a biological process in brain cell development that may help explain some causes of mental retardation. This understanding may one day help other researchers develop therapies that can reduce specific forms of retardation.

In a paper published in The Journal of Neuroscience, Rutgers cell biologists Hongxin Chen and Bonnie Firestein show that proteins of the Rho family, when excessively present in developing brain cells known as neurons, inhibit another protein that promotes healthy neuron development. Firestein earlier demonstrated how this protein, called cypin, promotes healthy branching patterns in the tree-like structures at the end of neurons that receive signals. Inadequate branching in these structures, called dendrites, has been observed in conditions such as Alzheimer’s disease, autism and some types of mental retardation.

“Imbalances of Rho proteins have been known to affect dendrite branching, and therefore have been implicated in causing mental retardation,” said Firestein, associate professor of cell biology and neuroscience. “How this happens, however, has not been clear. Now we’re seeing that Rho proteins signal other proteins downstream. In our case, we discovered that a type of Rho protein called RhoA is inhibiting cypin production when it is overactive or present in excess. The resulting lack of cypin is detrimental to healthy branching development in dendrites.”

Firestein and Chen, a postdoctoral research fellow, believe that this finding offers a new potential target for future drug therapies aimed at promoting healthier dendrite branching. “Scientists could try to block Rho activity, but since Rho is present in lots of different types of cells, reducing Rho activity could have widespread side effects,” said Firestein. “Looking for a protein that Rho is signaling to could result in a more targeted treatment.”

Cypin is restricted to a few regions in the brain, most notably the hippocampus, which controls learning and memory. Faulty dendrite branching there is likely to cause retardation. Therefore, a therapy that focuses specifically on development of hippocampal neurons might be more effective and less harmful to other organs and tissues.

Firestein first identified and isolated cypin in 1999, and has recently focused on how it works in the hippocampus. Cypin assembles protein molecules called tubulin into microtubules, which form the long chain molecules that are structural basis, or the “skeleton,” of a dendrite. An effective assembly process is needed to form the branching patterns needed for proper functioning.

Source: Rutgers, the State University of New Jersey

Related stories:

Normalizing tumor vessels to improve cancer therapy
Chemotherapy drugs often never reach the tumors they're intended to treat, and radiation therapy is not always effective, because the blood vessels feeding the tumors are abnormal—"leaky and twisty" in the words of the late Judah Folkman, MD, founder of the Vascular Biology program at Children's Hospital Boston.
Scientists trace causal link between a tumor suppressor gene and liver cancer
Scientists at Cold Spring Harbor Laboratory (CSHL) have taken the search for cancer-causing genes an important step forward. In a newly published paper, they confirm that a gene called DLC1 is a tumor suppressor. They have demonstrated in living mice that its deletion, inactivation or loss precipitates events culminating in an aggressive type of liver cancer closely related to common human epithelial cancers of the liver (also known as hepatocellular carcinoma, or HCC).
An ancient protein balances gene activity and silences foreign DNA in bacteria
Compared to humans, bacteria have a much tidier genome. The tiny microorganisms pack their genes closely together, and don’t carry around a lot of extraneous DNA, so-called junk DNA that fills in the gaps between genes. Some 90 percent of the complete genome sequence of the bacteria E. coli contains sequences of DNA that code for protein, while 90 percent of the human genome is non–coding junk DNA.
Extracellular protein sensitizes ovarian cancer cells to chemotherapy
Scientists have uncovered critical new details about the mechanisms that modulate the response of ovarian cancer cells to chemotherapy. The research, published by Cell Press in the December issue of Cancer Cell, helps to explain why many patients develop resistance to the taxane class of drugs and may lead to improved treatment of ovarian cancer.
Tiny Clue Reveals New Path Toward Heart Disease
Geneticists have discovered a new gene that may put individuals at higher risk of developing cardiovascular disease.
Researchers hot on the trail of brain cell degeneration
A research team headed by Academy Research Fellow Michael Courtney has identified a new molecular pathway in neurons. The pathway is a factor in the degeneration of brain cells, which in turn plays an important role in neurological conditions and diseases, such as Alzheimer's disease, epilepsy and stroke.
Nerve Cells' Power Plants Caught In A Traffic Jam
Nerve cells need lots of energy to work properly, and the energy needs to be delivered to the right place at the right time. By inducing a mutation in fruit flies, researchers have figured out that a particular gene governs the movement of cells' energy-producing units, called mitochondria.
Embryo implantation offers insight into infertility
(PhysOrg.com) -- A process that governs embryo implantation in the womb in humans has been identified for the first time. The Oxford University research, published in the journal PNAS, could shed light on what goes wrong when embryos fail to implant in the lining of the womb, a leading cause of infertility.

News discussion:

Medicine & Health news