• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 3
  • Tagged with
  • 3
  • 3
  • 2
  • 2
  • 2
  • 2
  • 2
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Cellular level/distribution of -secretase subunit nicastrin and its modulator p23 in the brain

Kodam, Anitha 06 1900 (has links)
The processing of amyloid precursor protein (APP) by - and -secretases produces amyloid (A) peptide, the principal component of the neuritic plaques found in Alzheimers disease (AD) pathology. The enzyme -secretase is a multimeric protein consisting of presenilins-1/2 (PS1/PS2), nicastrin, anterior pharynx defective 1 (APH-1) and presenilin enhancer-2 (PEN-2). Recently it was discovered that p23, a transmembrane protein involved in intracellular protein trafficking, negatively regulates -secretase activity. In the present study, I evaluated the levels/expression of the nicastrin and p23 and their possible colocalization with PS1 in normal adult and developing brains. Additionally, I have studied the alterations of p23 levels in both animal model of neurodegeneration and in postmortem AD brains. Nicastrin and p23 were widely distributed throughout the brain and colocalized in all brain regions with PS1. The levels of nicastrin and p23 were relatively high at the early stages of postnatal development and then declined gradually as age increased. Interestingly, p23 level/expression was found to be altered following kainic acid-induced neurodegeneration in the adult rat brain. Additionally, p23 levels were reduced in the brains of individuals with AD. These results, taken together, suggest that both nicastrin and p23 are expressed in neurons throughout the brain and their levels decline gradually during development to reach an adult profile. Additionally, my results indicate that a decreased level of p23 may contribute to AD pathogenesis by increasing the production of A-related peptides.
2

Cellular level/distribution of γ-secretase subunit nicastrin and its modulator p23 in the brain

Kodam, Anitha Unknown Date
No description available.
3

Modulation of γ-Secretase Activity by a Carborane-Based Flurbiprofen Analogue

Saretz, Stefan, Basset, Gabriele, Useini, Liridona, Laube, Markus, Pietzsch, Jens, Draˇca, Dijana, Maksimovi´c-Ivani´c, Danijela, Trambauer, Johannes, Steiner, Harald, Hey-Hawkins, Evamarie 05 May 2023 (has links)
All over the world, societies are facing rapidly aging populations combined with a growing number of patients suffering from Alzheimer’s disease (AD). One focus in pharmaceutical research to address this issue is on the reduction of the longer amyloid-β (Aβ) fragments in the brain by modulation of γ-secretase, a membrane-bound protease. R-Flurbiprofen (tarenflurbil) was studied in this regard but failed to show significant improvement in AD patients in a phase 3 clinical trial. This was mainly attributed to its low ability to cross the blood–brain barrier (BBB). Here, we present the synthesis and in vitro evaluation of a racemic meta-carborane analogue of flurbiprofen. By introducing the carborane moiety, the hydrophobicity could be shifted into a more favourable range for the penetration of the blood–brain barrier, evident by a logD7.4 value of 2.0. Furthermore, our analogue retained γ-secretase modulator activity in comparison to racemic flurbiprofen in a cell-based assay. These findings demonstrate the potential of carboranes as phenyl mimetics also in AD research.

Page generated in 0.083 seconds