Specific Domains of β-Amyloid from Alzheimer Plaque Elicit Neuron Killing in Human Microglia
| Autor: | Yu Min Kuo, Joel B. Kirkpatrick, Jun Li, Donald Tom, Alex E. Roher, Jiahan Yu, Lanny J. Haverkamp, William Karshin, Dana Giulian |
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| Rok vydání: | 1996 |
| Předmět: |
Neurotoxins
Inflammation Peptide Cell Communication Biology Alzheimer Disease β amyloid medicine Animals Humans Neurotoxin Senile plaques Neurons chemistry.chemical_classification Amyloid beta-Peptides Microglia General Neuroscience Articles Peptide Fragments Rats Blockade Cell biology medicine.anatomical_structure nervous system chemistry Neuron medicine.symptom Neuroscience |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | Alzheimer's disease (AD) is found to have striking brain inflammation characterized by clusters of reactive microglia that surround senile plaques. A recent study has shown that microglia placed in contact with isolated plaque fragments release neurotoxins. To explore further this process of immunoactivation in AD, we fractionated plaque proteins and tested for the ability to stimulate microglia. Three plaque-derived fractions, each containing full-length native A beta 1-40 or A beta 1-42 peptides, elicited neurotoxin release from microglia. Screening of various synthetic peptides (A beta 1-16, A beta 1-28, A beta 12-28, A beta 25-35, A beta 17-43, A beta 1-40, and A beta 1-42) confirmed that microglia killed neurons only after exposure to nanomolar concentrations of human A beta 1-40 or human A beta 1-42, whereas the rodent A beta 1-40 (5Arg--Gly, 10Tyr--Phe 13His--Arg) was not active. These findings suggested that specific portions of human A beta were necessary for microglia-plaque interactions. When coupled to microspheres, N-terminal portions of human A beta (A beta 1-16, A beta 1-28, A beta 12-28) provided anchoring sites for microglial adherence whereas C-terminal regions did not. Although itself not toxic, the 10-16 domain of human A beta was necessary for both microglial binding and activation. Peptide blockade of microglia-plaque interactions that occur in AD might prevent the immune-driven injury to neurons. |
| Databáze: | OpenAIRE |
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