Mood metal makes two-pronged attack on Alzheimer's disease
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For personal use. Only reproduce with permission from The Lancet Publishing Group. THE LANCET Neurology Vol 2 July 2003 http://neurology.thelancet.com 391 Newsdesk The foundation stone of the first Spanish centre specialising in the long- term rehabilitation of patients with multiple sclerosis (MS) was laid on May 19 in Madrid. The centre, which will open in the summer of 2004, will employ about 40 professionals, including neurologists specialising in rehabilitation, speech therapists, occu- pational therapists, and psychologists. The centre will offer training courses for health professionals involved in the care of patients with MS and will also support clinical and epidemiological research. The Centre for the Integral Rehabilitation of MS patients will be managed by the Spanish Association of Multiple Sclerosis (AEDEM). “We have received an unconditional grant from Madrid’s City Council”, says AEDEM spokeswoman Amparo Mínguez. The city council has donated a 3000 m 2 plot to AEDEM to construct the centre near the Ramón y Cajal Hospital. The Obra Social Caja de Madrid foundation will donate €1·5 million to build the centre, and ONCE, a Spanish national organisation for the blind, will provide the equipment, including two gymnasiums. AEDEM is a 20-year-old, non- profit organisation made up of 48 local associations. It provides information to newly diagnosed patients. “By positively modifying our mind and behaviour, MS will become a journey companion and not an unknown enemy—that’s our message to patients”, says Mínguez. Francisco Alcázar, a rehabilitation doctor at the nearby hospital, says the initiative, although isolated, is “great news” because patients with MS are not currently given sufficient long- term care. After a relapse, he says, patients “are transferred to a short- term rehabilitation centre and then go home until another relapse occurs”. Rehabilitation and psychological support are essential for both relapsing–remitting and progressive MS, notes Alcazar. Luis Gangoiti, a member of AEDEM’s advisory medical board, who also heads the Madrid-based Centre for Brain Damage, applauds the rehabilitation centre and notes that in addition to increased resources for patients with MS, the initiative will provide doctors with an opportunity to receive specialised training in rehabilitation. Xavier Bosch Spanish centre for rehabilitation of multiple sclerosis to be built New findings may help resolve the dispute on whether therapy for Alzheimer’s disease (AD) should target overproduction of tau protein found in neurofibrillary tangles or amyloid- peptide (A) in plaques. The answer, suggest researchers from University of Pennsylvania School of Medicine (Philadelphia, PA, USA), may be to inhibit an enzyme involved in both processes, which can be achieved with lithium—at least in an animal model. Previously, the team led by Peter Klein discovered that lithium inhibits glycogen synthase kinase-3 (GSK-3), which phosphorylates tau, and also interacts with presenilin. Mutated presenilin leads to increased A production. “We wanted to test whether GSK-3 might be involved in this process”, says Klein. “We inhibited GSK-3 with lithium and found that it indeed reduced production of A in vitro and in mice that overproduce A”. This effect was also seen with another inhibitor of GSK-3, while increased and decreased expression of another isoform, GSK-3, increased and decreased A production, respectively. Together, the studies indicate that GSK-3 is required for the processing of amyloid precursor protein (APP) into A by regulating -secretase, says James Woodgett (Ontario Cancer Institute, Toronto, Canada), who co- authored a commentary on the research. “The effect of the kinase on APP processing is selective in that -secretase activity towards Notch, another substrate of the secretase, is unaffected by inhibition of GSK-3”, he explains. This led Klein’s team to conclude that GSK-3 offers an attractive target for pharmacological agents aimed at reducing the formation of amyloid plaques and neurofibrillary tangles (Nature 2003; 423: 392–93, 435–50). Retrospective analysis of AD risk in people treated with lithium for bipolar disorder could provide further supportive evidence. But Woodgett believes that there is now justification to assess whether lithium treatment of patients predisposed to AD can act as a prophylactic for plaque formation and retard progression of the disease. “What isn’t known”, he says, “is whether clinically established dosages of lithium used in the treatment of bipolar disorder will be sufficient to prevent APP processing and plaque formation in people.” Since certain non-steroidal anti- inflammatory drugs similarly reduce A production, but via a different mechanism, combination therapy might further reduce amyloid accumulation. “Several companies have been developing small-molecule inhibitors of GSK-3”, Woodgett told The Lancet Neurology. These agents are not selective for or isoforms, but “since both forms of GSK-3 are implicated in the generation of hyperphosphorylated tau, this may be a good thing”, he says. Klein’s laboratory will now start searching for regulators of GSK-3. Kelly Morris Mood metal makes two-pronged attack on Alzheimer’s disease MS centre will open in the summer of 2004 AEDEM
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Transcript of Mood metal makes two-pronged attack on Alzheimer's disease
For personal use. Only reproduce with permission from The Lancet Publishing Group.
THE LANCET Neurology Vol 2 July 2003 http://neurology.thelancet.com 391
Newsdesk
The foundation stone of the firstSpanish centre specialising in the long-term rehabilitation of patients withmultiple sclerosis (MS) was laid onMay 19 in Madrid. The centre, whichwill open in the summer of 2004, will employ about 40 professionals,including neurologists specialising inrehabilitation, speech therapists, occu-pational therapists, and psychologists.The centre will offer training coursesfor health professionals involved in thecare of patients with MS and will alsosupport clinical and epidemiologicalresearch.
The Centre for the IntegralRehabilitation of MS patients will bemanaged by the Spanish Association ofMultiple Sclerosis (AEDEM). “We havereceived an unconditional grant fromMadrid’s City Council”, says AEDEMspokeswoman Amparo Mínguez. Thecity council has donated a 3000 m2 plotto AEDEM to construct the centre nearthe Ramón y Cajal Hospital. The ObraSocial Caja de Madrid foundation will
donate €1·5 million to build the centre, and ONCE, a Spanish nationalorganisation for the blind, will providethe equipment, including twogymnasiums.
AEDEM is a 20-year-old, non-profit organisation made up of 48 localassociations. It provides informationto newly diagnosed patients. “Bypositively modifying our mind andbehaviour, MS will become a journeycompanion and not an unknown
enemy—that’s our message topatients”, says Mínguez.
Francisco Alcázar, a rehabilitationdoctor at the nearby hospital, says theinitiative, although isolated, is “greatnews” because patients with MS arenot currently given sufficient long-term care. After a relapse, he says,patients “are transferred to a short-term rehabilitation centre and then gohome until another relapse occurs”.Rehabilitation and psychologicalsupport are essential for bothrelapsing–remitting and progressiveMS, notes Alcazar.
Luis Gangoiti, a member ofAEDEM’s advisory medical board,who also heads the Madrid-basedCentre for Brain Damage, applaudsthe rehabilitation centre and notes thatin addition to increased resources forpatients with MS, the initiative willprovide doctors with an opportunityto receive specialised training inrehabilitation.Xavier Bosch
Spanish centre for rehabilitation of multiple sclerosis to be built
New findings may help resolve thedispute on whether therapy forAlzheimer’s disease (AD) should targetoverproduction of tau protein foundin neurofibrillary tangles or amyloid-�peptide (A�) in plaques. The answer,suggest researchers from University ofPennsylvania School of Medicine(Philadelphia, PA, USA), may be toinhibit an enzyme involved in bothprocesses, which can be achieved withlithium—at least in an animal model.
Previously, the team led by PeterKlein discovered that lithium inhibitsglycogen synthase kinase-3 (GSK-3),which phosphorylates tau, and alsointeracts with presenilin. Mutatedpresenilin leads to increased A�production. “We wanted to testwhether GSK-3 might be involved inthis process”, says Klein. “Weinhibited GSK-3 with lithium andfound that it indeed reducedproduction of A� in vitro and in micethat overproduce A�”. This effect wasalso seen with another inhibitor ofGSK-3, while increased and decreased
expression of another isoform,GSK-3�, increased and decreased A�production, respectively.
Together, the studies indicate thatGSK-3� is required for the processingof amyloid precursor protein (APP)into A� by regulating �-secretase, saysJames Woodgett (Ontario CancerInstitute, Toronto, Canada), who co-authored a commentary on theresearch. “The effect of the kinase onAPP processing is selective in that�-secretase activity towards Notch,another substrate of the secretase, isunaffected by inhibition of GSK-3”, heexplains. This led Klein’s team toconclude that GSK-3� offers anattractive target for pharmacologicalagents aimed at reducing theformation of amyloid plaques andneurofibrillary tangles (Nature 2003;423: 392–93, 435–50).
Retrospective analysis of AD risk inpeople treated with lithium for bipolardisorder could provide furthersupportive evidence. But Woodgettbelieves that there is now justification
to assess whether lithium treatment ofpatients predisposed to AD can act as aprophylactic for plaque formation andretard progression of the disease.“What isn’t known”, he says, “iswhether clinically established dosagesof lithium used in the treatment ofbipolar disorder will be sufficient toprevent APP processing and plaqueformation in people.”
Since certain non-steroidal anti-inflammatory drugs similarly reduceA� production, but via a differentmechanism, combination therapymight further reduce amyloidaccumulation. “Several companieshave been developing small-moleculeinhibitors of GSK-3”, Woodgett toldThe Lancet Neurology. These agents arenot selective for � or � isoforms, but“since both forms of GSK-3 areimplicated in the generation ofhyperphosphorylated tau, this may bea good thing”, he says. Klein’slaboratory will now start searching forregulators of GSK-3�.Kelly Morris
Mood metal makes two-pronged attack on Alzheimer’s disease
MS centre will open in the summer of 2004
AED
EM
