EURON and THEME joint PhD meeting

Recommendations

Info

94 EURON and THEME joint meeting 2011 γ-secretase dependent phagocytosis of Amyloid-beta (Aβ) in microglial cells Sonia Tosheva, Jochen Walter Department of Neurology, University of Bonn. Introduction Alzheimer’s disease (AD) is the most common form of dementia characterized by key features that include neurofibrillary tangels formation and depositions of fibrillar amyloid β-peptides (Aβ) which form senile plaques in the brain. Aβ is produced after amyloid precursor protein proteolytic cleavage via β and γ-secretase pathways. γ-secretase cleaves many type I proteins thereby affecting the protein stability and trafficking, cognitive functions, intracellular signaling and calcium homeostasis. This enzyme is a complex of 4 individual proteins but the catalytic role is due to Presenilins (PS). And missense mutations in the PS genes are a major cause of early onset of familial AD (FAD). To address the critical role of γ-secretase in amyloid plaque clearance, we focused our work on studying the involvement of microglial cells in this process. The microglial phagocytosis of Aβ can be triggered via several receptors like the Low density lipoprotein receptor related protein1 (LRP1). LRP1 is a type I membrane protein and a γ-secretase substrate. It interacts with APP and facilitates its trafficking and processing. LRP1 uses Aβ as a ligand and controls its uptake and transport to the lysosomes. There Aβ is degraded by proteolitic enzymes mainly Cathepsin D. Methods We chose different approaches to study the γ-secretase functions in microglial cell lines- BV2 and ES derived microglia (EsDM). Genetic mutations of the Presenilin (PS) gene and pharmacological component (DAPT) were used to inhibit the γ-secretase activity. Results Our results showed that γ-secretase is involved in Aβ uptake and decrease in this process was seen after γ-secretase inhibition. We reported that Aβ`s receptor LRP1 is expressed in microglial cells where its processing and endocytosis is γ-secretase dependent. Cells with inhibited γ-secretase activity demonstrated impaired LRP1 endocytosis, and Aβ cellular uptake. This also correlated with a decrease in degradation and changes in the lysosomal structure and localization. Opposite effects were shown in microglia cells overexpressing PS1 where the rate of Aβ uptake and its degradation was significantly high.
95 EURON and THEME joint meeting 2011 Conclusion Our results indicate that γ-secretase inhibition contribute to Aβ accumulation in the brain. Modulation of γ-secretase activity could be used as a promising therapeutic target.
Page 1 and 2:
EURON and THEME joint PhD meeting U
Page 3 and 4:
The local organizing committee: Pro
Page 5 and 6:
Information about THEME 3 EURON and
Page 7 and 8:
5 EURON and THEME joint meeting 201
Page 9 and 10:
EURON a short introduction 7 EURON
Page 11 and 12:
Page 13 and 14:
Page 15 and 16:
Programme 13 EURON and THEME joint
Page 17 and 18:
Thursday September 22 nd 9:00 - 10:
Page 19 and 20:
Friday September 23 rd 17 EURON and
Page 21 and 22:
Poster presentations 19 EURON and T
Page 23 and 24:
Page 25 and 26:
EURON Lecture Frank Kirchhoff ADDRE
Page 27 and 28:
ABSTRACT 25 EURON and THEME joint m
Page 29 and 30:
THEME Lecture Eckhard Mandelkow POS
Page 31 and 32:
ABSTRACT 29 EURON and THEME joint m
Page 33 and 34:
Abstracts 31 EURON and THEME joint
Page 35 and 36:
33 Euron PhD meeting 2010 Methodolo
Page 37 and 38:
35 Euron PhD meeting 2010 Tcfap2c t
Page 39 and 40:
Page 41 and 42:
Page 43 and 44:
Page 45 and 46: 43 EURON and THEME joint meeting 20
Page 95: 93 EURON and THEME joint meeting 20
Page 105 and 106: List of Participants 103 EURON and
Page 107 and 108: Nuersailike Abuduwali University of
Page 109 and 110: Marianne Eisenhardt University of B
Page 111 and 112: Sabine Klein University of Bonn PhD
Page 113 and 114: Viktoriya Peeva University of Bonn
Page 115: Sylvie van der Kruijs Maastricht Un
show all

EURON and THEME joint PhD meeting

Create successful ePaper yourself

Delete template?

Save as template?