Computer simulations had predicted that amyloid fibrillogenesis is governed by free energy barriers and kinetic traps (kinetic control), rather than the free energy of the final aggregates. The simulations suggested that the diversity in fibril morphologies can originate from variations in the number of protofilaments which has been confirmed by recent cryo-electron microscopy studies of amyloid-β fibrils derived from brain tissue of Alzheimer's patients. The kinetic control of fibril formation and polymorphism imply that chemical substances with new mechanisms of action are needed to fight Alzheimer's disease.
BT - ACS Chemical Neuroscience C1 - 0251 DA - 2020 Jan 15 DO - 10.1021/acschemneuro.9b00676 IS - 2 J2 - ACS Chem. Neurosci. LA - eng M3 - Research Article N2 -Computer simulations had predicted that amyloid fibrillogenesis is governed by free energy barriers and kinetic traps (kinetic control), rather than the free energy of the final aggregates. The simulations suggested that the diversity in fibril morphologies can originate from variations in the number of protofilaments which has been confirmed by recent cryo-electron microscopy studies of amyloid-β fibrils derived from brain tissue of Alzheimer's patients. The kinetic control of fibril formation and polymorphism imply that chemical substances with new mechanisms of action are needed to fight Alzheimer's disease.
PY - 2020 SP - 103 EP - 104 T2 - ACS Chemical Neuroscience TI - Kinetic control of amyloidogenesis calls for unconventional drugs to fight Alzheimer's disease VL - 11 SN - 1948-7193 ER -