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April 28, 2009

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Insulin may help treat Alzheimer’s: researchers

Feb. 2, 2009
Courtesy Northwestern University
and World Science staff

Sci­en­tists are re­port­ing that in­su­lin, com­monly used to treat di­a­be­tes, may al­so pro­tect against Alz­heim­er’s dis­ease by pro­tect­ing com­muni­ca­tion junc­tions be­tween brain cells.

The find­ings sug­gest the dev­as­tat­ing mem­o­ry-robbing ill­ness could re­sult from a newly re­cog­nized form of di­a­be­tes,  said the re­search­ers, who re­port their work in the on­line edition for the week of Feb. 2 of the re­search jour­nal Pro­ceed­ings of the Na­tional Acad­e­my of Sci­ences. 

The study fo­cused on brain cells tak­en from the hip­po­cam­pus, one of the brain’s cru­cial mem­o­ry cen­ters. The in­ves­ti­ga­tors treated cells with in­su­lin and and found that it blocked dam­age to cells ex­posed to harm­ful pro­teins im­pli­cat­ed in Alz­heim­er’s, by keep­ing the pro­teins from latch­ing on­to the cells. They al­so found that this pro­tection could be en­hanced by rosigli­ta­zone, a type 2 di­a­be­tes drug.

Fu­ture ther­a­pies could in­volve mak­ing the brain more re­spon­sive to in­su­lin, a nat­u­rally pro­duced sub­stance, said the sci­en­tists. “Ther­a­peu­tics de­signed to in­crease in­su­lin sen­si­ti­vity in the brain could pro­vide new av­enues” for treat­ment, said Wil­liam L. Klein of North­west­ern Uni­ver­s­ity in Il­li­nois, the stu­dy’s sen­ior au­thor. 

The det­ri­men­tal mo­le­cules, called AD­DLs or am­y­loid beta-derived dif­fus­i­ble lig­ands, at­tack mem­o­ry-form­ing syn­apses, or com­mu­nica­t­ion junc­tions be­tween brain cells. Klein and col­leagues have found that the harm­ful pro­teins, once at­tached to syn­apses, strip cells of some of their in­su­lin re­cep­tors, sur­face struc­tures that re­spond to in­su­lin. 

This prob­lem can wors­en with age, he added; wheth­er some­one de­vel­ops Alz­heim­er’s may de­pend on how a molecular-level bat­tle be­tween AD­DLs and in­su­lin plays out. The lat­ter seems to pro­tect the syn­apses by set­ting in mo­tion events that re­duce the num­ber of sites on the syn­apse where ADDL can latch on.

The find­ing “of­fers new hope for fight­ing mem­o­ry loss in Alz­heim­er’s dis­ease,” said the stu­dy’s lead au­thor Fer­nan­da G. De Fe­lice, a form­er vis­it­ing sci­ent­ist in Klein’s lab now at the Fed­er­al Uni­ver­s­ity of Ri­o de Janeiro, Bra­zil.

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Scientists are reporting that insulin, commonly used to treat diabetes, may also protect against Alzheimer’s disease by shielding memory forming junctions between brain cells from harm. The findings suggest the devastating memory-robbing illness could be due to a novel third form of diabetes, which is treated by insulin, said the researchers. The researchers report their findings the week of Feb. 2 in the research journal Proceedings of the National Academy of Sciences online. The study focused on brain cells taken from the hippocampus, one of the brain’s crucial memory centers. The investigators treated cells with insulin and and found that it blocked damage to brain cells exposed to harmful proteins implicated in Alzheimer’s, by keeping the proteins from latching onto the cells. They also found that this protection could be enhanced by rosiglitazone, a type 2 diabetes drug. Future therapies could involve making the brain more responsive to insulin, a naturally produced substance, said the scientists. “Therapeutics designed to increase insulin sensitivity in the brain could provide new avenues for treating Alzheimer’s disease,” said William L. Klein of Northwestern University in Illinois, the study’s senior author. The detrimental molecules, called ADDLs or amyloid beta-derived diffusible ligands, attack memory-forming synapses, or communication junctions between brain cells. Klein and colleagues have found that the harmful proteins, once attached to synapses, strip cells of some of their insulin receptors, surface structures that respond to insulin. This problem can worsen with age, he added; whether someone develops Alzheimer’s may depend on how a molecular-level battle between ADDLs and insulin plays out. The latter seems to protect the synapses by setting in motion events that reduce the number of sites on the synapse where ADDL can latch on. The finding “offers new hope for fighting memory loss in Alzheimer’s disease,” said the study’s lead author Fernanda G. De Felice, a former visiting scientist in Klein’s lab now at the Federal University of Rio de Janeiro, Brazil.