Potential target for treating schizophrenia found
(Medical Xpress) -- Scientists at the University of Glasgow have identified a potential target for the treatment of schizophrenia.
Schizophrenia is a mental condition in which individuals experience a range of symptoms, including auditory hallucinations, paranoid delusions and muddled thought or speech.
It is one of the most common mental health conditions, affecting 2-4 people per 1,000 in the UK.
It is widely believed that a special protein called DISC1, which plays a key role in the development of the brain cortex, may be a susceptibility factor for schizophrenia, as well as mood disorders and autism.
The cortex is a part of the brain that plays a key role in memory, attention, awareness, thought, language and consciousness. While it is well-known that defects in this region are associated with schizophrenia, it is not understood how these defects develop.
DISC1 is a so-called signalling scaffold protein because it acts as a control centre by recruiting other types of proteins, attracting them to its surface where they generate and interpret signals able to control brain development and function.
Professor Miles Houslay, of the Institute of Neuroscience & Psychology at the University of Glasgow, said: While it is now well-recognised that DISC1 is a major susceptibility factor for these brain diseases, we still dont understand enough about the range of processes it controls and how they go wrong in mental illness.
However, as reported in the latest edition of the journal Nature, the Glasgow team, working with colleagues from John Hopkins University, Duke University and Keio University, Tokyo, have shown that DISC1 acts as a molecular switch that controls two key stages in the development of the cortex.
One stage involves how cells in the cortex multiply in development and the other stage relates to how brain cells migrate within the cortex to specific locations that allow for correct functioning.
Prof Houslay added: These processes are critical for normal brain function. However, as these new results show that DISC1 is a protein whose function can be dynamically regulated, it opens up the possibility of pharmaceutical and biotech companies designing new medicines able to correct defects in DISC1 that lead to the debilitating disease of schizophrenia.
Schizophrenia, mood disorders and autism cause great emotional and financial hardships for individuals, their families and for society as a whole. Because of this we desperately need to know what goes wrong in the brain that leads to these debilitating conditions.
More information: DISC1-dependent switch from progenitor proliferation to migration in the developing cortex, Nature, Volume: 473, Pages: 9296 Date published: 05 May 2011. DOI: doi:10.1038/nature09859 www.nature.com/nat… re09859.html
Regulatory mechanisms governing the sequence from progenitor cell proliferation to neuronal migration during corticogenesis are poorly understood. Here we report that phosphorylation of DISC1, a major susceptibility factor for several mental disorders, acts as a molecular switch from maintaining proliferation of mitotic progenitor cells to activating migration of postmitotic neurons in mice. Unphosphorylated DISC1 regulates canonical Wnt signalling via an interaction with GSK3β, whereas specific phosphorylation at serine 710 (S710) triggers the recruitment of BardetBiedl syndrome (BBS) proteins to the centrosome. In support of this model, loss of BBS1 leads to defects in migration, but not proliferation, whereas DISC1 knockdown leads to deficits in both. A phospho-dead mutant can only rescue proliferation, whereas a phospho-mimic mutant rescues exclusively migration defects. These data highlight a dual role for DISC1 in corticogenesis and indicate that phosphorylation of this protein at S710 activates a key developmental switch.
Provided by University of Glasgow
- New study solidifies role of DISC1 in risk for schizophrenia and other mental illness Apr 06, 2011 | not rated yet | 0
- Study sheds light on how psychiatric risk gene disrupts brain development Jul 14, 2010 | not rated yet | 0
- Genetic clues hold key to schizophrenia treatment Mar 20, 2009 | not rated yet | 0
- Schizophrenia gene linked with abnormal neurogenesis in adult and postnatal brain Sep 23, 2009 | not rated yet | 0
- Brain development switch could affect schizophrenia, other conditions Apr 06, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
By discovering the new mechanism by which estrogen suppresses lipid synthesis in the liver, UC Irvine endocrinologists have revealed a potential new approach toward treating certain liver diseases.
Medical research May 23, 2013 | 5 / 5 (1) | 0 |
Aortic arch pulse wave velocity, a measure of arterial stiffness, is a strong independent predictor of disease of the vessels that supply blood to the brain, according to a new study published in the June issue the journal ...
Medical research May 23, 2013 | not rated yet | 0
Since the discovery of Prontosil in 1932, sulfonamide antibiotics have been used to combat a wide spectrum of bacterial infections, from acne to chlamydia and pneumonia. However, their side effects can include serious neurological ...
Medical research May 23, 2013 | 3 / 5 (1) | 0 |
Scientists at the National Institutes of Health report they have discovered in mouse studies that a small molecule released in the spinal cord triggers a process that is later experienced in the brain as ...
Medical research May 23, 2013 | 5 / 5 (3) | 0 |
Spanish researchers have discovered that the daily clearance of neutrophils from the body stimulates the release of hematopoietic stem cells from the bone marrow into the bloodstream, according to a report published today ...
Medical research May 23, 2013 | 5 / 5 (2) | 0
Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality ...
10 hours ago | 5 / 5 (2) | 5
(HealthDay)—Animals make great companions for senior citizens, but elderly people who always drive with a pet in the car are far more likely to crash than those who never drive with a pet, researchers have ...
2 hours ago | not rated yet | 0
Heart failure accelerates the aging process and brings on early andropausal syndrome (AS), according to research presented today at the Heart Failure Congress 2013. AS, also referred to as male 'menopause', was four times ...
10 hours ago | not rated yet | 1
Mortality and length of stay are highest in heart failure patients admitted in January, on Friday, and overnight, according to research presented today at the Heart Failure Congress 2013. The analysis of nearly 1 million ...
10 hours ago | not rated yet | 0
(AP)—Department of Justice lawyers have again asked a federal appeals court in New York to delay lifting age restrictions and prescription requirements on an emergency contraceptive popularly known as the morning-after ...
10 hours ago | not rated yet | 0