Laboratoire Matière et Systèmes Complexes

Thèse de Chiho Watanabe effectuée sous la direction de Miglena Angelova, in collaboration with Dr. Nicolas Puff, Dr. Michel Seigneuret, Dr. Galya Staneva and Dr. David Tareste.

Soutenance le 2 septembre 2015 à 10 h.

Lieu : bâtiment Condorcet, salle 454A (bâtiment Condorcet) (niveau 4). La soutenance sera suivie d’un pot au 6e étage.

The diversity of lipids as regulator of membrane properties. Possible roles in Alzheimer’s disease.

Abstract : Alzheimer’s disease (AD) is a neurodegenerative disease, which is the most common form of dementia. The critical event in the pathogenesis is the accumulation of amyloid beta (Abeta) peptide. Finding the disease molecular mechanisms is essential for AD preventions and treatments. Many positive or negative correlations between AD development and specific lipids and their homeostasis have been found. This thesis is aimed to study Abeta interaction with model membrane systems containing specific lipids. We hypothesize that in vivo specific lipid homeostasis changes alters the fundamental membrane physical properties and amyloid beta (Abeta) peptide-membrane interactions. Such effects themselves modulate protein activities and protein expression, thereby leading to AD development with possible feedback to lipid homeostasis. We have found that sphingosine and sphingosine-1-phosphate, which are cell fate regulators participating to the “sphingolipid rheostat”, modulate membrane physicochemical properties in an antagonistic manner. Furthermore, the balance between the two lipids regulates the membrane interaction with amyloid beta (Abeta). We also find a lipid-composition-dependent effect of amyloid beta (Abeta) peptide in SNARE-associated membrane fusion important for neurotransmission. We have also studied the effect of the ganglioside GM1 on raft-like domain dynamics, as a preliminary study to that on the effect of amyloid beta (Abeta). These findings support the idea of the participation of specific lipids in Alzheimer’s disease pathology.

 References-

1) Puff N, Watanabe C, Seigneuret M, Angelova MI, Staneva G (2014) Biochim Biophys Acta (BBA) 1838:2105.

2) Watanabe C, Puff N, Staneva G, Seigneuret M, Angelova MI (2014) Langmuir 30 :13956.

3) Watanabe C, Puff N, Staneva G, Angelova MI, Seigneuret M (2015) Colloids & Surfaces A : Physicochemical and Engineering Aspects, in press, http://dx.doi.org/10.1016/j.colsurf...