Navigation Links
Parkinson's mutation stunts neurons

Mutations in a key brain protein known to underlie a form of Parkinson's disease (PD) wreaks its damage by stunting the normal growth and branching of neurons, researchers have found. They have pinpointed the malfunction of the protein made by mutant forms of the gene called LRRK2 and how it affects neurons, ultimately leading to their death. The loss of dopamine-producing neurons is central to the pathology of PD, and loss of connections among such neurons is an early feature of the PD disease process.

The researchers, Asa Abeliovich and colleagues at Columbia University, said their findings could lead to animal models for studying the form of PD and ultimately to new treatments for the disease. They reported their findings in the November 22, 2006, issue of the journal Neuron, published by Cell Press.

The researchers launched their study of LRRK2 because other scientists had identified mutations in the gene in an inherited form of PD that mimics the clinical and pathological features of the common sporadic form of the disease. LRRK2 stands for "leucine-rich repeat kinase-2," which means that the LRRK2 protein is an enzyme called a kinase--a biochemical switch that activates other proteins by attaching a molecule called a phosphate to them.

In their experiments, when the researchers generated mutant forms of the enzyme, they discovered that the mutants showed higher-than-normal enzymatic kinase activity compared to the normal version. When they introduced the mutant forms into cultures of neurons, they saw a reduction in the growth and branching of the neurons. Such growth is critical for the neurons to establish and maintain connections with one another in the brain's neural circuitry. The researchers also found that cultured neurons with mutant LRRK2 enzymes showed reduced survival.

The researchers analyzed the function of the mutant proteins, establishing that it was the "triggering" kinase segment of the protein that was cen tral to the enzyme's defective function.

The pathology of PD caused by mutated LRRK2 also includes formation of abnormal deposits, or "inclusions," in the neurons. Similarly, Abeliovich and his colleagues found that the mutant LRRK2 proteins they created also caused such inclusions in the brain cell cultures.

What's more, when the researchers introduced the mutant form of LRRK2 into the adult rat brain, they saw the same stunting of growth of dopamine-producing neurons and production of abnormal inclusions. Finally, when they introduced the mutant LRRK2 into embryonic rat brain, they saw a reduction of length and branching of neuronal wiring during brain development.

The researchers wrote that their findings offer "a useful animal model for early LRRK2-associated disease." They concluded that their techniques of introducing the mutated gene could lead to a primate model for the form of PD. "These cellular and animal models may promote the discovery of effective therapeutics for LRRK2-associated disease," they wrote.
'"/>

Source:Cell Press


Related biology news :

1. Scientists detect probable genetic cause of some Parkinsons disease cases
2. Gene Therapy For Parkinsons Disease Moves Forward In Animals
3. Duke Chemists Isolating Individual Molecules Of Toxic Protein In Alzheimers, Parkinsons Disease
4. Gene therapy for Parkinsons disease moves forward in animals
5. Neurologix announces positive results of gene therapy clinical trial in Parkinsons disease
6. Renewed hope for Parkinsons patients
7. Amphetamines reverse Parkinsons disease symptoms in mice
8. UCLA scientists find male gene in brain area targeted by Parkinsons
9. Gene therapy turns off mutation linked to Parkinsons disease
10. Key stress protein linked to toxicities responsible for Parkinsons, Alzheimers
11. Parkinsons disease mechanism discovered

Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/29/2016)... RATON, Florida , March 29, 2016 ... or the "Company") LegacyXChange "LEGX" and SelectaDNA/CSI Protect are ... DNA in ink used in a variety of writing ... theft. Buyers of originally created collectibles from athletes on ... through forensic analysis of the DNA. ...
(Date:3/22/2016)... PUNE, India , March 22, 2016 ... new market research report "Electronic Sensors Market for ... Fingerprint, Proximity, & Others), Application (Communication & ... and Geography - Global Forecast to 2022", ... consumer industry is expected to reach USD ...
(Date:3/21/2016)... Massachusetts , March 22, 2016 ... facial recognition with passcodes for superior security   ... ), a leading provider of secure digital communications services, ... their biometric technology and offer enterprise customers, particularly those ... secure facial recognition and voice authentication within a mobile ...
Breaking Biology News(10 mins):
(Date:4/26/2016)... (PRWEB) , ... April 27, 2016 , ... ... of Lewis Roca Rothgerber Christie LLP as an associate in the firm’s Intellectual ... and international electrical, mechanical and electromechanical patent applications. He has an electrical engineering ...
(Date:4/26/2016)... Heidelberg, Baden-Württemberg (PRWEB) , ... April 26, 2016 ... ... production of laser lithography systems, announces the latest technology innovation for its Volume ... to fulfill tomorrow’s demand for production of advanced photomasks as well as a ...
(Date:4/26/2016)... ... April 26, 2016 , ... BioFactura, Inc ., a biopharmaceutical research ... financing. Healthy investor interest drove significant oversubscription of the original $1.5M target. ... biosimilars, to the advanced preclinical stages. , Chief Executive Officer and President, Darryl ...
(Date:4/26/2016)... ... April 26, 2016 , ... uBiome, the leading microbial genomics company, welcomes ... company’s Advisory Board. Prior to co-founding Plum in 2007, Neil Grimmer was Vice President ... , A renowned, innovative designer of ideas, products, and brands, Grimmer has been at ...
Breaking Biology Technology: