Amyloid Pores

Protein aggregation, more specifically amyloid fibril formation, has been implicated as a primary cause of neurodegeneration in Alzheimer’s disease (AD), Parkinson’s disease (PD), and related disorders. In amyloid fibril formation, a protein undergoes conformational changes either before or coincident with its self-assembly into highly ordered β-sheet-rich aggregates, referred to as amyloid fibrils. Amyloid fibrils are typically deposited in the brain and/or in peripheral tissues and have been linked to neurodegeneration and/or organ dysfunction by genetic, pathological and biochemical evidence.

The identification and characterization of neurotoxic quaternary structure intermediates, referred to as protofibrils, that precedes fibril formation, combined with the observation that several pathogenic mutations promote protofibril formation, suggest that the protofibrils, rather than the fibrils, are the pathogenic species in these diseases. However, the exact mechanisms by which protofibrils and/or fibrils induce cytotoxicity and/or neurodegeneration remain controversial. Therefore, a detailed understanding of the mechanism of amyloid fibril formation and its relation to disease pathology should contribute to our understanding of the mechanism of pathogenesis and the design of effective therapeutic strategies to treat and/or prevent these devastating diseases.

The Amyloid Pores Team (2002)

Front row (L-R):
June Park, Richard Nowak, Magdalena Anguiano,
Dean Hartley, Michael Volles, Hilal Lashuel

Back row (L-R):
Christophe Rochet, Benjamin Petre, Tom Walz,
Peter Lansbury, Jeffrey Kessler, Tomas Ding

α-Synuclein	β-Amyloid
Serum Amyloid A	Superoxide Dismutase