Phenylketonuria is one of the most common inherited metabolic disorders (1:10,000 births). A new paradigm for the aetiopathology of phenylketonuria suggests the presence of amyloidlike Phenylalanine assemblies in the brains of transgenic mouse models and patients, possibly shedding light on the selective cognitive deficit associated with this disease. We performed cellular toxicity, X-Ray and microscopy experiments focused on Phenylalanine aggregation mechanism and cytotoxicity. Phenylalanine has been observed to not aggregate in water over long periods, whereas a pronounced propensity to surfaces has been observed, promoting fast aggregation and fibril formation. The extent and effect of interaction of Phe with whole membranes or with membrane lipids is still unexplored. Assessing their mutual structural interaction could provide a clue towards understanding the mechanism of PKU. We plan to investigate by SANS, the interaction of Phe with different model membranes, with biomimetic composition, in bulk solution. The effect of an interfering molecule, as a possible drug, will also be exploited.

Investigation of Phenylketonuria molecular basis : focus on phenylalanine interaction with model membranes / P. Brocca, V.M. Rondelli, I. Grillo, E. DEL FAVERO, C. Laura. - (2016). [10.5291/ill-data.8-03-893]

Investigation of Phenylketonuria molecular basis : focus on phenylalanine interaction with model membranes

Paola Brocca;Valeria Rondelli;Elena Del favero;Laura Cantu
2016

Abstract

Phenylketonuria is one of the most common inherited metabolic disorders (1:10,000 births). A new paradigm for the aetiopathology of phenylketonuria suggests the presence of amyloidlike Phenylalanine assemblies in the brains of transgenic mouse models and patients, possibly shedding light on the selective cognitive deficit associated with this disease. We performed cellular toxicity, X-Ray and microscopy experiments focused on Phenylalanine aggregation mechanism and cytotoxicity. Phenylalanine has been observed to not aggregate in water over long periods, whereas a pronounced propensity to surfaces has been observed, promoting fast aggregation and fibril formation. The extent and effect of interaction of Phe with whole membranes or with membrane lipids is still unexplored. Assessing their mutual structural interaction could provide a clue towards understanding the mechanism of PKU. We plan to investigate by SANS, the interaction of Phe with different model membranes, with biomimetic composition, in bulk solution. The effect of an interfering molecule, as a possible drug, will also be exploited.
Settore FIS/07 - Fisica Applicata(Beni Culturali, Ambientali, Biol.e Medicin)
https://hdl.handle.net/2434/704731
https://hdl.handle.net/2434/805539
https://hdl.handle.net/2434/859737
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/925244
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