Antibodies to synthetic fragment 95–123 of the prion protein protect neurons and astrocytes from beta-amyloid toxicity

Molecular mechanisms of β-amyloid toxic effect on brain cells during Alzheimer’s disease is associated with oxidative stress, intracellular Ca²⁺ increase in neurons and astrocytes and activation of reactive oxygen species production. Prion protein is known to be involved in beta-amyloid toxicity. Here we investigated an effect of affinity purified antibodies to synthetic fragment 95–123 of the prion protein (PrP-(95–123)) on β-amyloid induced cell death, Ca²⁺-signal, reactive oxygen species production and caspase 3 activation. We have shown that antibodies to PrP-(95–123) are able to protect neurons and astrocytes from beta-amyloid induced cell death with no effect on the intracellular Ca²⁺ concentration altered by beta-amyloid treatment. However, the antibodies significantly reduced β-amyloid induced reactive oxygen species production in astrocytes and decreased caspase 3 activation in neurons and astrocytes. Thus, induction of antibodies to PrP-(95–123) of the prion protein provides a new approach to anti-Alzheimer’s disease vaccine design.