• ArtsandLectures twitter avatar
    RT @terragalleria: FYI “Treasured Lands” sold out in a month from publisher & Amazon, 3rd party copies may not last long https://t.co/MIV5v…
    10 hours 13 min ago
  • UCSBgauchos twitter avatar
    .@UCSBMensSoccer shuts out Sac State to clinch fourth straight @BigWestMSOC North Title, first round bye! RECAP >>>… https://t.co/1UbVzyLJAh
    11 hours 42 min ago
  • UCSBgauchos twitter avatar
    No. 5 UCSB Moves Up Two Spots In Rankings Heading Into Matchup With No. 18 UCI https://t.co/CDVMIkaUY4
    13 hours 6 sec ago
  • ucsantabarbara twitter avatar
    #UCSB ranks No. 24 among the top 1,000 universities in the world! #GoGauchos #BestGlobal https://t.co/s2bWeN56By
    13 hours 44 min ago
  • ArtsandLectures twitter avatar
    RT @nehalPjoshi: Saw #sellbuydate a few weeks ago & still marveling at @jonesarah. Every actor should see her specific meticulous work. @M
    14 hours 59 min ago
  • ArtsandLectures twitter avatar
    RT @terragalleria: RT @vcstar Nature photographer Q.T. Luong will be at UCSB Nov. 2, sharing his work. https://t.co/mNUnQhBUJC
    15 hours 27 sec ago
  • ArtsandLectures twitter avatar
    A great introduction to the music & magic of @NekoCase: The 12 Best Neko Case Songs, according to @pastemagazine https://t.co/M4rwUM8dfh
    15 hours 1 min ago
  • UCSBgauchos twitter avatar
    UCSB Finishes 9th at Saint Mary's Invitational; Swanson is 9th https://t.co/XzcXoykWFn
    15 hours 59 min ago
  • ArtsandLectures twitter avatar
    Funk titan @MaceoParker is opening up his sound check to the public. See a living legend at work, tomorrow at 4pm!… https://t.co/HGABPXjm5z
    16 hours 23 min ago
  • UCSBgauchos twitter avatar
    UCSB Picked 4th in Big West Media Poll; Vincent Named to Preseason All-Conference Team https://t.co/sOYy2LdUiF
    16 hours 33 min ago
  • UCSBgauchos twitter avatar
    .@UCSBMensSoccer vs. Sacramento State is live! Audio: https://t.co/NWB5rDzaIb Live Stats: https://t.co/Dseq5Dl4Ro
    16 hours 45 min ago
  • UCSBgauchos twitter avatar
    .@UCSBMensSoccer clinches Big West North title, bye in 1st rd of Big West Tourney w/ win or draw at Sac State!
    16 hours 51 min ago
  • UCSBgauchos twitter avatar
    .@UCSBMensSoccer Starting XI vs. Sac St: Le Roux, Pero, Quezada, Salgado, Perez, Ilskens, Batista, Feucht, Pando, DePuy, Selemani
    16 hours 52 min ago
  • UCSB_GradPost twitter avatar
    Stress less in grad school! https://t.co/MMWLr9EwyV #UCSB #ucsbgradpost
    18 hours 11 min ago
  • ArtsandLectures twitter avatar
    Preview the amazing story of the rebirth of Africa's lost Eden, #Gorongoza, with @BobPoole's stunning footage https://t.co/sRrodm1gpF
    19 hours 33 min ago

Mouse Models Point To A Potential Therapeutic Approach for Alzheimer's

The findings demonstrate a new potential target in the fight against Alzheimer’s and other neurodegenerative diseases
Wednesday, June 26, 2013 - 17:00
Santa Barbara, CA

Tau Zhang.jpg

Neurofibrillary tangles

Neurofibrillary tangles, immunostained bright red in pyramidal neurons here, are one of the hallmarks of Alzheimer’s disease.

Photo Credit: 

Israel Hernandez, UCSB

Ken Kosik.jpeg

Kenneth S. Kosik

Kenneth S. Kosik

Kosik researchers.jpg

Hernandez and Zhang

Israel Hernandez and Xuemei Zhang

Photo Credit: 

George Foulsham

Building on research published eight years ago in the journal Chemistry and Biology, Kenneth S. Kosik, Harriman Professor in Neuroscience and co-director of the Neuroscience Research Institute (NRI) at UC Santa Barbara, and his team have now applied their findings to two distinct, well-known mouse models, demonstrating a new potential target in the fight against Alzheimer's and other neurodegenerative diseases.

The results were published online June 4 as the Paper of the Week in the Journal of Biological Chemistry. As a Paper of the Week, Kosik's work is among the top 2 percent of manuscripts the journal reviews in a year. Based on significance and overall importance, between 50 and 100 papers are selected for this honor from the more than 6,600 published each year.

Kosik and his research team focused on tau, a protein normally present in the brain, which can develop into neurofibrillary tangles (NFTs) that, along with plaques containing amyloid-ß protein, characterize Alzheimer's disease. When tau becomes pathological, many phosphate groups attach to it, causing it to become dysfunctional and intensely phosphorylated, or hyperphosphorylated. Aggregations of hyperphosphorylated tau are also referred to as paired helical filaments.

"What struck me most while working on this project was how so many people I'd never met came to me to share their stories and personal anxieties about Alzheimer's disease," said Xuemei Zhang, lead co-author and an assistant specialist in the Kosik Lab. "There is no doubt that finding therapeutic treatment is the only way to help this fast-growing population." Israel Hernandez, a postdoctoral scholar of the NRI and UCSB's Department of Molecular, Cellular and Developmental Biology, is the paper's other lead co-author.

Treatments for hyperphosphorylated tau, one of the main causes of Alzheimer's disease, do not exist. Current treatment is restricted to drugs that increase the concentration of neurotransmitters to promote signaling between neurons.

However, this latest research explores the possibility that a small class of molecules called diaminothiazoles can act as inhibitors of kinase enzymes that phosphorylate tau. Kosik's team studied the toxicity and immunoreactivity of several diaminothiazoles that targeted two key kinases, CDK5/p25 and GSK3ß, in two Alzheimer's disease mouse models. The investigators found that the compounds can efficiently inhibit the enzymes with hardly any toxic effects in the therapeutic dose range.

Treatment with the lead compound in this study, LDN-193594, dramatically affected the prominent neuronal cell loss that accompanies increased CDK5 activity. Diaminothiazole kinase inhibitors not only reduced tau phosphorylation but also exerted a neuroprotective effect in vivo. In addition to reducing the amount of the paired helical filaments in the mice's brains, they also restored their learning and memory abilities during a fear-conditioning assay.

According to the authors, the fact that treatment with diaminothiazole kinase inhibitors reduced the phosphorylation of tau provides strong evidence that small molecular kinase inhibitor treatment could slow the progression of tau pathology. "Given the contribution of both CDK5 and GSK3ß to tau phosphorylation," said Kosik, "effective treatment of tauopathies may require dual kinase targeting."

Madison Cornwell, a Beckman Scholar with UCSB's Center for Science and Engineering Partnerships who worked in Kosik's lab, added: "As a beginning step, we demonstrated that two of these compounds were successful in clearing the brain of tau tangles in a mouse model, but someday inhibitors of these kinases may serve to ameliorate the symptoms of Alzheimer's disease in patients."

Neuroscience Research Institute

Contact Info: 

Julie Cohen julie.cohen@ia.ucsb.edu (805 893-7220