By Monika L. S. Robbins, CONTRIBUTING WRITER
The anti-inflammatorydrug ibuprofen may act as a neuroprotective agent against the risk ofParkinsons disease, according to researchers at the Harvard School ofPublic Health.
In the observational study, participants who regularlyused ibuprofen were 40 percent less likely to develop Parkinsonsdisease over a six-year period, according to lead researcher Xiang Gao,an instructor in medicine at HSPH.
These findings confirmed theresults of a 2005 study that found that users of non-steroidal,anti-inflammatory drugsincluding ibuprofendisplayed a lower risk ofdeveloping Parkinsons disease.
The current study focused onibuprofen, which can be purchased over the counter in the form ofpopular brands such as Advil.
Over six years, 130,000 subjectsself-reported their health statuses and specifically noted their use ofibuprofen and whether they had been diagnosed with Parkinsons disease.
Thestudy found that 15 to 20 percent of participants regularly usedibuprofen, and 291 individuals were diagnosed with the disease withinthe six-year timeframe.
Despite the suggestions of a correlationbetween ibuprofen use and risk of Parkinsons disease, the Harvardresearchers said that the studys findings cannot be used to reach anyconclusions because the research was purely observational and did notexamine causality.
The next step is to take advantage of thestudys findings by further exploring the relationship between ibuprofenuse and risk of Parkinsons disease, said Michael A. Schwarzschild, anassociate professor of neurology at Harvard Medical School and one ofthe studys authors.
Schwarzschild said that it is not surprisingthat anti-inflammatory medication like ibuprofen may help reduce therisk of the disease, which involves inflammation of the brain. Butscientists have yet to determine exactly why ibuprofen may be moreeffective as a neuroprotective agent than other anti-inflammatory drugs,Schwarzschild explained.
Parkinsons disease is a chronicneurological disorder that progressively slows down movement. Dubbedthe shaking palsy by its discoverer James Parkinson, the disease ischaracterized by a rest tremor, a steady shaking that typically beginsin one hand while a patient is at rest, according to Schwarzschild.
Thedisease is also associated with dementia, depression, and otherdisorders. According to the National Parkinson Foundation, 60,000 newcases of Parkinsons disease are diagnosed each year.
The studywhichwill be presented in April at the American Academy of Neurology meetingin Torontoalso involved researchers Honglei Chen and Alberto Ascherio,a professor of epidemiology and nutrition at HMS.

By MARIA CHENG AP Medical Writer 2010 The Associated Press

LONDON When it comes to the placebo effect, it really may be mind over matter,a new analysis suggests.
In a review of recent research,international experts say there is increasing evidence that faketreatments, or placebos, have an actual biological effect in the body.
Thedoctor-patient relationship, plus the expectation of recovery, maysometimes be enough to change a patient's brain, body and behavior,experts write. The review of previous research on placebos was publishedonline Friday in Lancet, the British medical journal.
"It's not thatplacebos or inert substances help," said Linda Blair, a Bath-basedpsychologist and spokeswoman for the British Psychological Society.Blair was not linked to the research. "It's that people's belief ininert substances help."
While doctors have long recognized thatplacebos can help patients feel better, they weren't sure if thetreatments sparked any physical changes.
In the Lancet review,researchers cite studies where patients with Parkinson's disease weregiven dummy pills. That led their brains to release dopamine, afeel-good chemical, and also resulted in other changes in brainactivity.
"When you think you're going to get a drug that helps, yourbrain reacts as if it's getting relief," said Walter Brown, a clinicalprofessor of psychiatry at Brown and Tufts University. "But we don'tknow how that thought that you're going to get better actuallytranslates into something happening in the brain."
With growing proofthat placebos work, some doctors are trying to figure out how tocapitalize on their effects, without being unethical.
Blair said thatto be completely honest with patients to tell them they werereceiving a fake treatment would sabotage their belief in the drug,and thus, undermine any potential benefit.
But Brown didn't agree.For certain patients, like those with mild depression or anxiety, hesaid placebos were likely to work just as well as established therapies.
Hesaid that even if doctors acknowledge they are giving such patients aplacebo medication, but say it could be beneficial, "it might justactually work."

Scientists have just identified several molecules capable of reversingthe brain abnormalities of Parkinsons disease (PD), while alsouncovering new clues for its origin in a study just published in thejournal Disease Models and Mechanisms (1). PD is characterised byabnormal deposits of a brain protein called alpha-synuclein throughoutthe damaged brain regions, but exactly what they do there is not clear.The fact that their numbers and spreading are associated diseaseprogression has made them, however, a major point of interest in PDresearch. The work now published suggests that these deposits areactually a normal physiological process to purge unwanted proteins but,when overloaded, they can also cause of the cellular abnormalitiesseen in PD neurons and, ultimately, neural death. This would explainwhy the disease tends to appear later in life when the whole metabolism(including this mechanism) becomes less efficient, and also why neuronsare particularly susceptible as they are one of the few cells of thebody that are not replaced when old and less capable. The study uses ayeast model of PD showing once again the power of simple organismmodels in the understanding of extremely complex human diseases.

PDis neurodegenerative disease characterised by increasing motor problems- tremors, rigidity and balance and coordination problems - that canleave the patient incapable of perform the simplest of everyday task.Many patients also suffer from non-motor symptoms, including dementia.There is also widespread death of dopamine-producing (dopaminergic)neurons in a part of the brain called the substantia nigra. Sincedopamine acts as messenger between this region (the control centre) andother neurons around the body to ensure proper regulation of the bodysmovement, these deaths are believed to cause PD motor disability.

Althoughthe symptoms can be treated with dopamine replacement therapies, as thedisease progresses, they stop working and, more importantly, PD is,ultimately, incurable. With the spread of the disease throughout anincreasing aging human population bringing dramatic financial andsocial costs (who will take care of these millions of patients?), newtreatments and/or a cure are now being exhaustively researched.

Amajor focus of the research has been a brain protein of unknownfunction called alpha-synuclein. In fact, deposits of abnormally foldedalpha-synuclein (a certain folding is associated to the properfunctioning of each protein) are found in inclusions dispersed all overthe damaged brain areas of PD patients. The role of these inclusions indisease is not known with hypotheses ranging from having no importance,to contribute to neural death or even serve to avoid death by renderingharmless toxic misfolded proteins. What is known, however, is thatthese alpha-synuclein inclusions are excellent markers of diseaseprogression they accompany the brain degeneration.

In 2003Tiago Outeiro - a Portuguese scientist and one of the first authors ofthe new study - and Susan Lindquist the team leader in both studies created a yeast model of PD by inserting the alpha-synuclein gene inyeast, an organism that normally does not have the protein. Remarkably,this created in yeast some of the cellular abnormalities seen in PDaffected neurons. And as alpha-synuclein quantities increased, also thenumbers of inclusions containing the protein, in such a way that ledthe researchers to suggest that these were, in fact, a physiologicalprocess for getting rid of unwanted proteins. And that maybe PDappeared when the capacity of the system was exceed. This hypothesiswas supported by the fact that multiplications of the normalalpha-synuclein gene (leading to protein overproduction) were known tocause some forms of human PD, and also by the disease tendency for alate onset, probably due to an aging and less metabolically capablebody.

To test this possibility in the study now published,Linhui Julie Su, Pavan K. Auluck, Tiago Fleming Outeiro and SusanLindquist, working at the Whitehead Institute for Biomedical Research,Cambridge USA, created yet another yeast PD model this time with evenhigher levels of alpha-synuclein (High-syn) by inserting extra copiesof the gene in the yeast genome. This PD model was then compared withyeast producing none or intermediate levels of alpha-synuclein(Int-syn) (this last organism was the one used in the 2003 study)

Remarkably,the new High-syn yeast suffered from several more of the cellularabnormalities characteristic of PD than the Int-syn yeast. The newabnormalities included problems with mitochondria (the energy producingfactories of the cell) as well as accumulation of toxic free radicals,in addition to the abnormalities in lipid transport mechanisms alreadydetected in Int-syn yeast. Problems in mitochondria and accumulation offree radicals are particularly interesting as, although seen in many PDpatients, until now they had been impossible to link toalpha-synuclein.

Next, to exploit the fact that the new(High-syn ) yeast PD model shared so many cellular features with itshuman counterpart the researchers tried to look for possible therapies.For that Su, Auluck and Outeiro tested 115,000 bioactive (so known toaffect live cells) compounds and found several able to correct one ormore of the cellular abnormalities induced by the high levels ofalpha-synuclein. Not only that, but these molecules were also effectivetreating worm and mammals (rat) models of PD. Even more remarkably,they were capable of rescuing human dopaminergic neurons in a third PDmodel raising the possibility that they could be used to treat human PD.

Interestinglyseveral of these new potentially therapeutic molecules looked verysimilar, what led Su and colleagues to test them against each other tofind that, in fact, they acted on the same targets across the differentspecies tested. This was particularly important because it shows thatthe biological mechanisms affected by the over-accumulation ofalpha-synuclein are conserved throughout millions of years of evolution- from yeast to humans further supporting the hypothesis that PDresults from a dysfunction of basic cellular mechanisms.

Inconclusion Su, Auluck and Outeiros work supports the idea thataccumulation of alpha-synuclein in vesicles inside brain cells, sotypical of PD, is a normal physiological mechanism, most probably toget rid of abnormal proteins. Overload of this mechanism seems enoughto cause PD-like symptoms (after all in these yeast models the proteinis perfectly normal). Neurons are particularly susceptible not onlybecause they are not renewed throughout the organisms life, but alsobecause they have higher than normal requirements for both mitochondriaand lipid metabolism due to their highly energetic functions.

Thenew studys major breakthrough, however, is the identification ofseveral new compounds apparently capable of reversing the cellularabnormalities associated with PD and, as such, with potential to beused in treatments against the brain degeneration of PD.

Infact, at the moment the disease is believed to already affect astriking 3% of the population above 65 years old (more than 1 millionin the US, 1,2 millions in Europe) and in a world where life expectancyis steadily increasing, pushing PD numbers (by the age of 80 more than2 out of 100 people will have signs of the condition), any clues intothe disease mechanisms and possible treatments are crucial.

Still,much more work is needed before therapies can be developed The nextstep - says Tiago Outeiro - is to confirm these results in other PDmodels, even more similar to the human disease, to understand betterthe mechanisms and identify the molecules targets so they can, ifproven secure, be eventually tested in humans

By Kate Devlin,

Parkinsons disease progresses more slowly inpatients with naturally high levels of the acid which triggers gout,suggesting a possible new treatment for the disease.

Patientswith high levels of uric acid were a third less likely to needtreatment over the course of two years than those with low levels, theresults of a new study show.

Researchers are now testing whether increasing Parkinsons patients uric acid levels safely can help their condition.

An antioxidant, the acid is created naturally as we digest food.

But too much uric acid, or urate, can cause bouts of gout, an extremely painful joint condition, and kidney stones.

Dietsrich in liver, seafood and dried beans have been linked to high uricacid levels but researchers warn that because of the side effectspatients should not try to increase their urate levels themselves.

Asmaller study published last year also suggested that high uric acidlevels could slow the progression of Parkinsons Disease.

DrAlberto Ascherio, from the Harvard School of Public Health, who led thestudy, said: Only now we can be reasonably sure that the slower rateof progression in patients with higher concentrations of urate is realand not a chance occurrence."

However, the researchers stressthat they do not yet know if it is the acid itself which carries theprotective benefit or some other process of the body which producesuric acid as a by-product.

The latest research looked at 800 sufferers of the condition.

Thelink between high uric acid levels and a slower development of thedisease was less clear in women then men, the study found, however thismay be because women tend to have higher natural levels of the acid.

Theresearchers are now conducting a trial to give 90 patients a drug,inosine, which can elevate uric acid levels, to test whether they canbe safely raised and if this slows the speed of the disease.

"Becauseelevated urate levels have known health risks, including gout andkidney stones urate elevation should only be attempted in the contextof a closely monitored clinical trial in which potential benefits andrisks are carefully balanced," Dr Schwarzschild said.

Author: Shamim ShaikhLouise Nicholson

Exposure to toxins /chemicals is considered to be a significant risk factor in thepathogenesis of Parkinson's disease (PD); one putative chemical is thenaturally occurring herbicide rotenone that is now used widely inestablishing PD models. We, and others, have shown that chronic lowdose rotenone treatment induces excessive accumulation of ReactiveOxygen Species (ROS), inclusion body formation and apoptosis indopaminergic neurons of animal and human origin.

Some studieshave also suggested that microglia enhance the rotenone inducedneurotoxicity. While the effects of rotenone on neurons are wellestablished, there is little or no information available on the effectof rotenone on microglial cells, and especially cells of human origin.

Theaim of the present study was to investigate the effects of chronic lowdose rotenone treatment on human microglial CHME-5 cells.

Methods:We have shown previously that rotenone induced inclusion body formationin human dopaminergic SH-SY5Y cells and therefore used these cells as acontrol for inclusion body formation in this study. SH-SY5Y and CHME-5cells were treated with 5nM rotenone for four weeks.

At the endof week 4, both cell types were analysed for the presence of inclusionbodies, superoxide dismutases and cell activation (only in CHME-5cells) using Haematoxylin and Eosin staining, immunocytochemical andwestern blotting methods. Levels of active caspases and ROS (both extraand intra cellular) were measured using biochemical methods.

Conclusion:The results suggest that chronic low dose rotenone treatment activateshuman microglia (cell line) in a manner similar to microglia of animalorigin as shown by others.

However human microglia releaseexcessive amounts of ROS extracellularly, do not show excessive amountsof intracellular ROS and active caspases and most importantly do notshow any protein aggregation or inclusion body formation. Humanmicroglia appear to be resistant to rotenone (chronic, low dose)induced damage.