Promising research on the susceptibility to and drug targets for Parkinson's disease

Mar 21, 2008

Better understanding of Parkinson’s disease onset during aging is important for improving diagnostics and developing strategies for therapeutic intervention. Scientists from the University Medical Center in Groningen have now identified genes and processes that may underlie what makes some people more susceptible to this disease. Their findings are described in an article published March 21 in the open-access journal PLoS Genetics.

On average, the population of the western world is living longer, resulting in an increased number of people with age-related neurological conditions, including Alzheimer’s and Parkinson’s disease. A cure for these diseases remains elusive because their molecular cause is only partially understood. It has been noted, however, that accumulations of folded proteins are commonly found within the brain cells of those who suffer from these diseases. For this reason “protein misfolding” seems to form the basis of these diseases.

To gain insight into the cellular processes that play a role in protein misfolding, the research group, led by Ellen Nollen, looked for genes in the round worm Caenorhabditis elegans that, if switched off, cause the number of inclusions to increase. During the course of their research, the scientists individually switched off 17,000 of the 19,000 genes and studied the effect on protein formation.

The study findings indicate that the gene sir-2.1 has a considerable effect on protein formation. In humans, this gene, called SIRT1, is evolutionarily conserved and is involved in the aging of yeast, flies, and worms and probably also in mammals. It lengthens the lifespan of worms by the activation of various routes through which signals are transmitted (stress response and insulin signal transduction). These findings suggest that sir 2.1 may represent a possible mechanistic relationship between aging and Parkinson's disease.

The accumulation of proteins has been shown to be strongly age-dependent and to occur in clearly distinguishable phases. From RNA-interference screening, it appears that the manner in which proteins accumulate in the roundworm model can be clearly differentiated from that of other diseases in which the aggregation of proteins occurs. Moreover, it shows a clear link with the aging process, in which the membranes of the endoplasmatic reticulum/Golgi system of the cell probably play a role. This study points the way towards further clarification of the pathological mechanisms of, and the genetic susceptibility to, Parkinson's disease and other conditions in which the disease-specific protein alpha-synuclein plays a role.

Citation: van Ham TJ, Thijssen KL, Breitling R, Hofstra RMW, Plasterk RHA, et al. (2008) C. elegans Model Identifies Genetic Modifiers of a-Synuclein Inclusion Formation During Aging. PLoS Genet 4(3): e1000027. doi:10.1371/journal.pgen.1000027

Source: Public Library of Science

Explore further: Genetic testing in kids is fraught with complications

Related Stories

A tale of two roads into protein unfolding

May 11, 2015

You are taking a class on origami and Mr. Otaki asks you to fold that little red piece of paper into a very elaborate design. You have to do it in a very short time. You try your best but you fail. Your origami ...

Protein aggregates save cells during aging

May 08, 2015

As an organism ages, a gradual loss of cellular protein quality control occurs. This results in the increased production of toxic protein clumps, so-called aggregates. Using a comprehensive approach, researchers ...

Functional nerve cells from skin cells

May 21, 2014

A new method of generating mature nerve cells from skin cells could greatly enhance understanding of neurodegenerative diseases, and could accelerate the development of new drugs and stem cell-based regenerative ...

Recommended for you

Genetic testing in kids is fraught with complications

Jul 02, 2015

A woman coping with the burden of familial breast cancer can't help but wonder if her young daughter will suffer the same fate. Has she inherited the same disease-causing mutation? Is it best to be prepared ...

Cause of acute liver failure in young children discovered

Jul 02, 2015

Acute liver failure is a rare yet life-threatening disease for young children. It often occurs extremely rapidly, for example, when a child has a fever. Yet in around 50 percent of cases it is unclear as to why this happens. ...

Genome sequencing illuminates rare Aicardi syndrome

Jul 02, 2015

As my inbox fills with ever more updates on the number of human genomes sequenced and the plummeting time and cost of next next next generation sequencing, I find myself hitting delete more and more often. ...

User comments : 0

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.