Parkinson's disease: Parkin protects from neuronal cell death

Researchers from Ludwig-Maximilians-Universitaet (LMU) in Munich identify a novel signal transduction pathway, which activates the parkin gene and prevents stress-induced neuronal cell death.

Parkinson's disease is the most common movement disorder and the second most common neurodegenerative disease after Alzheimer's disease. It is characterized by the loss of dopamin-producing neurons in the , a region in the midbrain, which is implicated in motor control. The typical clinical signs include resting tremor, muscle rigidity, slowness of movements, and impaired balance. In about 10% of cases Parkinson's disease is caused by mutations in specific genes, one of them is called parkin.

"Parkinson-associated genes are particularly interesting for researchers, since insights into the function and dysfunction of these genes allow conclusions on the pathomechanisms underlying Parkinson's disease", says Dr. Konstanze Winklhofer of the Adolf Butenandt Institute at the LMU Munich, who is also affiliated with the German Center for (DZNE). Winklhofer and her colleagues had previously observed that parkin can protect neurons from cell death under various . In the course of this project, it became obvious that a loss of parkin function impairs the activity and integrity of mitochondria, which serve as the cellular power stations. In their latest publication, Winklhofer and coworkers uncovered the that accounts for parkin's neuroprotective action.

"We discovered a novel signaling pathway that is responsible for the neuroprotective activity of parkin," Winklhofer reports. The central player of this pathway is a protein called NEMO, which is activated by the enzymatic attachment of a linear chain of ubiquitin molecules. This reaction is promoted by parkin, thereby enabling NEMO to activate a signal cascade, which ultimately leads to the expression of a specific set of genes. Winklhofer's team identified one essential gene targeted by this pathway, which turned out to code for the mitochondrial protein OPA1. OPA1 maintains the integrity of mitochondria and prevents stress-induced .

"These findings suggest that strategies to activate this signal pathway or to enhance the synthesis of OPA1 in cells exposed to stress could be of therapeutic benefit," Winklhofer points out.

The newly identified signal pathway may also be relevant in the context of other neurological conditions that are characterized by the loss of specific neurons. Konstanze Winklhofer and her group are already engaged in further projects designed to determine whether other molecules regulated by this pathway might provide targets for therapeutic interventions.

add to favorites email to friend print save as pdf

Related Stories

When cells run out of fuel

Aug 24, 2009

Parkinson's disease is caused by the degeneration of neurons in the midbrain. The mechanisms leading to the loss of these neurons, however, are largely unknown. Recent research revealed that about ten per cent of cases are ...

New insight into Parkinson's disease

Apr 19, 2010

New research provides crucial insight into the pathogenic mechanisms of Parkinson's disease (PD), a prevalent neurodegenerative disorder. The study appears in the April 19 issue of the Journal of Cell Biology.

Recommended for you

Parkinson's disease reverted at a experimental stage

20 hours ago

Mexican scientists demonstrated experimentally, with adult rats, that mobility can be restored in patients with Parkinson's disease, the major degenerative disease of the motor system worldwide. The experiments ...

EU team launches clinical trial of Parkinson's vaccine

Dec 09, 2014

Today the EU-consortium SYMPATH starts recruitment for a Phase I study of a Parkinson's vaccine candidate called AFFITOPE PD03A. This vaccine is one out of a designated pool of promising vaccine candidates based on AFFiRiS' ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.