This title appears in the Scientific Report :
2014
Please use the identifier:
http://hdl.handle.net/2128/9165 in citations.
Pharmakokinetic properties of D-peptides developed to be therapeutically active against beta-amyloid oligomers
Pharmakokinetic properties of D-peptides developed to be therapeutically active against beta-amyloid oligomers
Alzheimer's disease (AD) is a neurodegenerative disorder and the most common type of dementia. To date, no curative treatment exists. Over 35 million people worldwide currently suffer from dementia and as the population ages numbers increase as well as the urgency to develop adequate therapeuti...
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Personal Name(s): | Hofmann, Leonie |
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Jiang, Nan / Kutzsche, Janine / Mauler, Jörg / Jürgens, Dagmar / Langen, Karl-Josef / Willuweit, Antje / Willbold, Dieter (Corresponding Author) | |
Contributing Institute: |
Strukturbiochemie; ICS-6 |
Published in: | 2014 |
Imprint: |
2014
|
Conference: | NeuroVisionen 10, Jülich (Germany), 2014-09-26 - 2014-09-26 |
Document Type: |
Poster |
Research Program: |
Structural Biology |
Link: |
OpenAccess |
Publikationsportal JuSER |
Alzheimer's disease (AD) is a neurodegenerative disorder and the most common type of dementia. To date, no curative treatment exists. Over 35 million people worldwide currently suffer from dementia and as the population ages numbers increase as well as the urgency to develop adequate therapeutics. An important part of the AD pathology is marked by beta-amyloid (Abeta) deposits, called plaques. Denantiomeric peptides (D-peptide) were developed that specifically reduce Abeta oligomers which are thought to be the most toxic species. D-peptides are less immunogenic and better protease-resistant than L-peptides, therefore thought to remain longer in the body providing more time to be therapeutically active. Here, we show pharmacokinetic studies of one of those D-peptides. The peptide's distribution through the body was assessed for the most important organs such as liver, kidney, brain and plasma. To do so, radioactively labelled peptide was administered via several administration routes and organs were harvested at different time points. The amount of D-peptide in the organ homogenate was measured by scintillation counting. Furthermore, binding to plasma proteins as well as brain membranes was determined, also using radioactively labelled peptide as indicator. Results show that the D-peptide indeed reaches the brain where it is thought to exhibit its therapeutic function. Furthermore, a long half-life and small elimination constant in plasma as well as a good bioavailability confirm the peptide's value as AD-therapeutic on its way to clinical studies. |