Related Experiment Video

Updated: Aug 1, 2026

Protein Misfolding Cyclic Amplification of Prions
10:12

Protein Misfolding Cyclic Amplification of Prions

Published on: November 7, 2012

Increase of intracellular free Ca2+ in microglia activated by prion protein fragment

J W Herms1, A Madlung, D R Brown

  • 1Department of Neuropathology, University of Göttingen, Germany.

Glia
|October 23, 1997
PubMed

Insights

The prion protein fragment PrP106-126 activates microglia, causing calcium level changes. This early cellular response is crucial for understanding neurodegeneration mechanisms.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Prion protein (PrPc) fragments, specifically PrP106-126, are known to be neurotoxic.
  • Microglia activation is implicated in the neurotoxic effects of PrP106-126.
  • Understanding the initial cellular events in microglia activation is essential.

Purpose of the Study:

  • To investigate the effect of the synthetic prion protein fragment PrP106-126 on intracellular free calcium concentration ([Ca2+]i) in cultured microglia.
  • To elucidate the role of extracellular calcium in the microglial response to PrP106-126.
  • To examine if the activation state of microglia influences their response to PrP106-126.

Main Methods:

  • Cultured microglia from wild-type and PrPc gene-ablated (Prn-p0/0) mice were used.
  • Intracellular free calcium concentration ([Ca2+]i) was measured using Fura-2.
  • Microglia were exposed to the PrP106-126 peptide, with and without extracellular calcium, and also after LPS treatment.

Main Results:

  • Both wild-type and Prn-p0/0 microglia showed an increase in [Ca2+]i upon exposure to PrP106-126 within 30 minutes.
  • Two types of calcium responses were observed: a small, transient, extracellular calcium-independent increase, and a strong, permanent, extracellular calcium-dependent increase.
  • The strong calcium increase was significantly less frequent in Prn-p0/0 cells, and LPS-activated microglia showed a reduced response rate.

Conclusions:

  • The prion protein fragment PrP106-126 triggers an early intracellular calcium increase in microglia.
  • A portion of the microglial response to PrP106-126 is dependent on extracellular calcium, suggesting involvement of calcium channels.
  • These findings represent the earliest known microglial reaction to a neurotoxic prion protein fragment.

More Related Videos

Monitoring Cell-to-cell Transmission of Prion-like Protein Aggregates in Drosophila Melanogaster10:26

Monitoring Cell-to-cell Transmission of Prion-like Protein Aggregates in Drosophila Melanogaster

Published on: March 12, 2018

Adipose-Derived Mesenchymal Stromal Cells Co-Cultured with Primary Mixed Glia to Reduce Prion-Induced Inflammation10:40

Adipose-Derived Mesenchymal Stromal Cells Co-Cultured with Primary Mixed Glia to Reduce Prion-Induced Inflammation

Published on: August 11, 2023

Related Concept Videos

Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Feedback Regulation of Calcium Concentration01:27

Feedback Regulation of Calcium Concentration

Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...