Prion-like behavior of amyloid-beta

Kim J, Holtzman DM (2010). Science, 330(6006):918-9 Read More

Abstract

Can certain neurodegenerative diseases be transmitted between humans by an infectious agent? The discovery that protein particles called prions can enter healthy mammals, including humans, and trigger a cascade of endogenous protein misfolding associated with bovine spongiform encephalopathy (“mad cow disease”) and Creutzfeldt-Jakob disease, certainly demonstrates this in prion diseases. Remarkably, neuronal proteins such as tau, α-synuclein, and polyglutamine aggregates, which are causally implicated in the neurodegenerative disorders Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, respectively, can be released from donor cells and taken up by neighboring acceptor cells. Moreover, treatment with exogenous misfolded neuronal proteins, such as tau, can trigger the misfolding and aggregation of their properly folded endogenous counterparts in host cells and animals (1). Besides prions, there is yet no evidence that other neurodegenerative diseases associated with protein misfolding are transmissible between humans by an infectious agent. But on page 980 in this issue, Eisele et al. (2) report that peripherally injected (outside the brain) mouse brain lysates containing aggregates of amyloid-β (Aβ)—the peptide that induces the formation of debilitating brain plaques in Alzheimer’s disease—causes plaque-associated pathological changes in the brains of recipient mice. This has implications for a pathogenic mechanism reminiscent of prion transmission.

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Posted on November 14, 2010
Posted in: HPAN, Neurodegeneration, Publications, Therapeutics & Diagnostics Authors: ,