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Posts Tagged ‘Alzheimer’

‘B’exarotene to become double ‘B’lock-buster – What are the chances?

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, Cell Biology, Signaling & Cell Circuits, Chemical Biology and its relations to Metabolic Disease, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Genome Biology, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Analytics, Pharmaceutical R&D Investment, Uncategorized, tagged Alzheimer, Alzheimers Disease, Apolipoprotein E, Beta amyloid, Bexarotene, Case Western Reserve University on June 7, 2012| Leave a Comment »

A recent study by researchers at Case Western Reserve University is likely to promise a new life to Alzheimer’s victims and their loved ones.

Alzheimer’s disease (AD) is associated with impaired clearance of β-amyloid (Aβ) from the brain, a process normally facilitated by apolipoprotein E (apoE). Oral administration of the retinoid X receptors (RXRs) agonist bexarotene to a mouse model of AD resulted in enhanced clearance of soluble Aβ within hours in an apoE-dependent manner. Aβ plaque area was reduced more than 50% within just 72 hours. Furthermore, bexarotene stimulated the rapid reversal of cognitive, social, and olfactory deficits and improved neural circuit function.

Thus, researchers hope and believe that, RXR activation stimulates physiological Aβ clearance mechanisms, resulting in the rapid reversal of a broad range of Aβ-induced deficits in humans as well.

Bexarotene has been approved for the treatment of cancer by the U.S. Food and Drug Administration for more than a decade. It has a good safety and side-effect profile, which researchers hope will help speed the transition to clinical trials of the drug.

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Reported by: Dr. V. S. Karra, Ph.D

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Insight into how cholesterol promotes amyloidogenesis

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, Cell Biology, Signaling & Cell Circuits, Chemical Biology and its relations to Metabolic Disease, Chemical Genetics, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Genome Biology, Personalized and Precision Medicine & Genomic Research, Pharmacotherapy of Cardiovascular Disease, tagged Alzheimer, Alzheimers Disease, Amyloid precursor protein, Cholesterol, Conditions and Diseases, Electron paramagnetic resonance, Gamma secretase, health on June 1, 2012| 2 Comments »

Enzymes act on the APP (Amyloid precursor protein) and cut it into fragments of protein, one of which is called beta-amyloid and its crucial in the formation of senile plaques in Alzheimer (Photo credit: Wikipedia)

C99 is the transmembrane carboxyl-terminal domain of the amyloid precursor protein that is cleaved by γ-secretase to release the amyloid-β polypeptides, which are associated with Alzheimer’s disease. Nuclear magnetic resonance and electron paramagnetic resonance spectroscopy show that the extracellular amino terminus of C99 includes a surface-embedded “N-helix” followed by a short “N-loop” connecting to the transmembrane domain (TMD). The TMD is a flexibly curved α helix, making it well suited for processive cleavage by γ-secretase. Titration of C99 reveals a binding site for cholesterol, providing mechanistic insight into how cholesterol promotes amyloidogenesis. Membrane-buried GXXXG motifs (G, Gly; X, any amino acid), which have an established role in oligomerization, were also shown to play a key role in cholesterol binding. The structure and cholesterol binding properties of C99 may aid in the design of Alzheimer’s therapeutics.

Source

Reported by: Dr. V. S. Karra, Ph.D