NWPF

News ArchivesRead News

Parkinson’s Mutation Stunts Neurons

Thursday November 30, 2006

24 Nov 2006(Medical News Today) - 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 central 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.

Recent News

Jul 24 - Parkinson's: Mutant gene interaction may pave the way for new treatments
Jul 22 - Boxing training used to fight against Parkinson's disease
Jul 17 - Stem cell treatment breakthrough could cure Parkinson’s patients
Jul 14 - Cancer drug shows early promise for Parkinson's disease
Jul 13 - Opinion: Dividing the Caregiving Responsibilities Between Siblings
Jul 12 - Researchers make advance in possible treatments for Gaucher, Parkinson’s diseases
Jul 11 - Parkinson’s Head Trauma Link Looks Even Stronger
Jul 7 - Penn students’ start-up XEED puts wearables to work against Parkinson’s disease
Jul 5 - Last Patient Enrolled in Pivotal Phase 3 Parkinson’s Disease Trial, Cynapsus Therapeutics Says
Jun 29 - Exoskeleton Could Quell the Tremors of Parkinson's Disease Patients at Crucial Moments
Jun 28 - Parkinson's disease: New protein discovery could fuel new treatments
Jun 27 - Study finds direct evidence linking Parkinson’s to autoimmune disease; 2 genes that are key regulators of immune system discovered
Jun 27 - Blocking key enzyme halts parkinson's disease symptoms in mice
Jun 23 - Parkinson's Research Might Benefit from Novel Discovery of Zinc Transport Protein Structure
Jun 23 - Parkinson's disease breakthrough 'could lead to cure'
Jun 20 - More American men diagnosed with Parkinson's
Jun 15 - First monkey genetically engineered to have Parkinson’s created
Jun 14 - Fighting Parkinson's in the lab
Jun 9 - A New Gene Has Been Linked to Parkinson's Disease
Jun 6 - A neurologist weighs in on Muhammad Ali's battle with Parkinson's disease