This website uses cookies to ensure you get the best experience on our website.
- Table of Contents
Facts about Disrupted in schizophrenia 1 protein.
Plays a role as a modulator of the AKT-mTOR signaling pathway controlling the speed of the process of toddlers integration during adult neurogenesis, such as neuron placement, dendritic development and synapse formation. Inhibits the activation of AKT-mTOR signaling upon interaction with CCDC88A.
Human | |
---|---|
Gene Name: | DISC1 |
Uniprot: | Q9NRI5 |
Entrez: | 27185 |
Belongs to: |
---|
No superfamily |
C1orf136; DISC1; disrupted in schizophrenia 1 protein; disrupted in schizophrenia 1; FLJ13381; FLJ21640; FLJ25311; FLJ41105; KIAA0457; SCZD9
Mass (kDA):
93.611 kDA
Human | |
---|---|
Location: | 1q42.2 |
Sequence: | 1; NC_000001.11 (231626790..232041272) |
Ubiquitous. Highly expressed in the dentate gyrus of the hippocampus. Also expressed in the temporal and parahippocampal cortices and cells of the white matter.
Cytoplasm. Cytoplasm, cytoskeleton. Mitochondrion. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cell junction, synapse, postsynaptic density. Colocalizes with NDEL1 in the perinuclear region and the centrosome (By similarity). Localizes to punctate cytoplasmic foci which overlap in part with mitochondria (PubMed:12506198, PubMed:15797709). Colocalizes with PCNT at the centrosome (PubMed:18955030).
We will examine the glycoprotein complex DISC1, a surrogate marker for DMD. Although the marker has been used in research studies there are some problems with it. Read on to learn why it is an ideal choice for clinical studies. The DISC1 is one of the most abundant proteins in the human body, so its use in research studies is particularly beneficial.
The pathophysiology behind schizophrenia is linked to the DISC1 genes. The DISC1 Protein functions as an adaptor, linking neuronal traffic to the motor machine. Mutations in the gene can cause mutations that alter the dopaminergic- and GABAergic pathways of mice. It has a wide range of roles in the brain. DISC1 may be found both in the nucleus or in neuronal cell membranes.
Cross-seeding the polyQ expanded mutant HTT with DISC1 increased aggregation. Transmission electron microscope revealed the formation aggregates DISC1-BSA. MALDITOF mass-spectrometry confirmed that aggregates contained a core containing two hydrogenatoms. These results support the hypothesis that DISC1 forms naturally in the human body.
DISC1 controls trafficking in amyloid precursor (APP), a neuronal vesicle residents transmembrane-protein implicated with the pathophysiology for Alzheimer's. Knockdown of DISC1 decreased APP internalization and increased its surface expression, affecting amyloid beta generation and proteolytic processing. It regulates transport of APP from axons via kinesin-1 motor, and the cJun-aminoterminal kinase interfacing protein 1 (cJAKIP1).
DISC1 regulates neurotransmission through interaction with Miro, a calcium binding protein with guanosine-triphosphate-like domains. DISC1 also interacts directly with trafficking kinesin bind protein 1/2, linking cargo and kinesin motors. The DISC1 mutation in point impairs synaptic travel in axons. DISC1 is also required for dendritic outgrowth in cultured cells.
DISC1 is responsible for the regulation of PDE4 in the brain. This was not known previously. Studies on HTT513 mutants have shown that it regulates PDE4 activity but only partially. HTT513 is more interconnected with DISC1 than ever thanks to polyQ expansion. Further studies are needed in order to determine if polyQ plays a part in the HTT/DISC1 interaction.
Surrogate markers are often used in drug trials. They are useful when the drug's effect upon surrogate measures is expected to be statistically meaningful or similar to what was intended. Surrogate measures can be used to stop a clinical trial or speed up the development life-saving treatments. FDA approval of drugs based on surrogate measures is the norm in several diseases. Surrogate measures have been used in seven out of the nine FDA approved drugs in the last five-years. Surrogates were used for all 26 diabetes drugs approved during that time. Of course, the approvals for all nine glaucoma drugs were based on surrogate measures. These measurements didn't accurately predict the efficacy, or the actual outcomes in patients.
A biomarker such as DISC1 may not be a reliable surrogate marker for clinical trials. The increase in this protein is due to increasing tumor burden. The relationship between DISC1-related disease progression is not always clear. To establish a link between the surrogate indicator and clinical benefit, it would be necessary to have credible epidemiologic proof. These markers cannot be used for determining if a particular drug will increase the disease progression.
The use of surrogate markers for clinical trials is critical for drug development. They allow us to predict the effects of a drug before it has been fully tested. Surrogate endpoints can help drug development go more efficiently. A surrogate marker that a drug's effect has on a clinical outcome, such as stroke, is a reduction of systolic (systolic) blood pressure. Trials of new drugs can be started earlier and in smaller numbers by using surrogate endpoints.
Steven Boster founded Boster Bio in 1993. He is known for his reputation of turning science in the lavatory into science. Boster's first products included a variety of primary antibodies and products for IHC, allowing him to build a catalog antibody company in China by the late 90s. Boster then developed a proprietary ELISA platform named PicoKine (tm), which provided high-sensitivity ELISA tests.
PMID: 10814723 by Millar J.K., et al. Disruption of two novel genes by a translocation co-segregating with schizophrenia.
PMID: 12573262 by Taylor M.S., et al. Evolutionary constraints on the Disrupted in Schizophrenia locus.
*More publications can be found for each product on its corresponding product page