Cell type specific uptake and clearance of wita-amyloid peptides

• Autorzy: Kuszczyk M. , Sadowski
• Języki publikacji: EN

Abstrakty

EN

Aggregation of β-amyloid peptides (Aβs) into toxic oligomers, amyloid fi brils, and its deposition in senile plaques initiate the neurodegenerative cascade of Alzheimer`s disease. Intraneuronal accumulation of Aβs starts prior to the appearance of senile plaques, and contributes to neurodegeneration by affecting protein traffi cking, mitochondrial metabolism, tau phosphorylation, and synaptic plasticity. The aim of this study was to compare the uptake and clearance of Aβs by various cell lines. SK-N-SH neuroblastoma cells rapidly metabolized Aβ clearing 40 μM of Aβ40 from the medium within 48 h. Pulse-uptake experiment demonstrated that Aβ40 was totally metabolized inside SK-NSH cells within 6 h. Presence of apolipoprotein E4 accelerated the Aβ40 uptake. In comparison, primary hippocampal neurons internalized only small fraction of Aβ40 present in the medium but showed notable intraneuronal Aβ40 accumulation. In pulseuptake experiment, intraneuronal presence of Aβ40 monomers and oligomers could be demonstrated after 24 h. Accumulation of Aβ40 by hippocampal neurons affected cell viability and membrane integrity as determined by MTT and LDH release assays, respectively. Our results demonstrate that neuroblastoma cells internalize and metabolize Aβ40 more effi ciently than primary hippocampal neurons. Therefore, under conditions of elevated Aβ level, hippocampal neurons are susceptible to Aβ accumulation and intraneuronal oligomerization what leads to downstream toxic effects.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 3
• Opis fizyczny: p.341

Twórcy

autor

Kuszczyk M.

• Department of Neurology, New York University School of Medicine, New York, NY, USA
• Department of Neurochemistry, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland

autor

Sadowski

• Department of Neurology, New York University School of Medicine, New York, NY, USA