A Small Slice of Parkinson's Research

Looking in to the energetic world of research into Parkinson's disease, it's easy to see progress in the works. Parkinson's is a "simple" condition in that it stems from the degeneration of a small, specific population of neurons - in that, it is better understood than a good many other neurodegenerative conditions. It is also probably closer to being prevented and cured; "all" that has to be done is to find some sustainable way to restore these cells, or prevent this specific damage from happening in the first place. That would seem to be a task well matched against the first generation of truly effective regenerative medicine, and I'd be willing to wager on a cure leaving the labs within the next decade.

Here are a couple of pieces illustrative of the present state of research:

Promising results from first gene therapy clinical trial for Parkinson's disease reported:

The study of 11 men and one woman with the progressive neurodegenerative illness found that the procedure -- in which surgeons inject a harmless gene-bearing virus into the brain -- was both safe and resulted in improved motor function for Parkinson's patients over the course of one year.

...

"In Parkinson's disease, not only do patients lose many dopamine-producing brain cells, but they also develop substantial reductions in the activity and amount of GABA in their brains. This causes a dysfunction in brain circuitry responsible for coordinating movement," Dr. During explains.

The researchers' bold idea: to insert the GABA-producing gene GAD back into an area of the brain called the subthalamic nucleus, a key regulatory center within this motor circuit.

"Our hope was that with a single operation to this single site, we could boost GABA production and thereby normalize the function of the entire circuit," Dr. Kaplitt says. "Not only would this alter the chemical balance in the subthalamic nucleus; it should also provide GABA to other parts of the network that weren't getting enough of the neurotransmitter."

Bigger Is Better; A New Therapeutic Approach For Parkinson's Disease:

The study shows how inhibition of SIRT2 - a member of the sirtuin family, which is linked to aging - prevents the toxicity of the protein aggregates that are believed to be behind the neuronal death characteristic of [Parkinson's disease]. Interestingly, and contrarily to "classic" approaches that try to eliminate these aggregates, SIRT2 inhibition appears to work by "fusing" many small protein aggregates into larger (apparently less neuro-toxic) ones.

...

SIRT2 is a member of the sirtuin family recently described as "the anti-aging proteins" as they seem to be capable of increase the life span of a multitude of organisms. In fact, SIRT1, one of its best-known members, is increased in the presence of anti-oxidants and during caloric restriction, both conditions known to increase longevity. SIRT2, however, seemed to have the opposite effect since its inhibition diminished the number of dead dopaminergic neurons in the presence of toxic alpha-synuclein aggregates.

I pointed out research on calorie restriction and alpha-synclein not so long ago. Given all the evidence linking calorie restriction to resistance to a number of age-related diseases, it should not be surprising to find that sirtuins have their hands in a lot of molecular mechanisms.

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