Amyloid plaques are no longer regarded as the pathogenic forms of Alzheimer's beta amyloid peptide (Abeta). Instead, small oligomers of amyloid proteins (Abeta and alpha-synuclein) that form Ca2+ permeable channels (amyloid pores) are now considered as the most neurotoxic species of amyloid proteins in neurodegenerative disorders. By disrupting Ca2+ homeostasis in brain cells, amyloid oligomers induce dramatic synaptic dysfunctions, impaired plasticity and neuronal degeneration. Hence, the oligomer model has all but supplanted the classical amyloid cascade.
Our group demonstrated that amyloid pores are formed by a common mecanism that can be summarized in three steps: 1- binding of the amyloid protein to the plasma membrane of a brain cell through a primary interaction with a ganglioside (GM1 or GM3) followed by 2- cholesterol-assisted insertion and 3- oligomerization into a Ca2+ permeable pore (Di Scala et al., Sci Rep. 2016, 6: 28781).
Elucidating this universal mechanism allowed us to create the first inhibitor of amyloid pore formation, now called AmyP53, that is active against wild-type and mutant forms of the proteins involved in Alzheimer's and Parkinson's diseases. A full description of the anti-pore properties of this inhibitor has been published here.
AmyP53 is not only one of the first molecules that target the oligomer cascade, it is the only one that can block the formation of the neurotoxic oligomers in the plasma membrane of brain cells.
AmyP53 now tested in animals by AmyPore!
MTD and DRF studies in male and female rats
No toxicity at 80 mg/kg by intravenous administration
No toxicity at 5 mg/kg by nasal administration
Now ready for nasal spray formulation!
Our work on the molecular organization of lipid rafts quoted in Wikipedia
(ref. 8 here)
J. Fantini H-index: 56
10000 visitors milestone reached!
L3 PGF Students
15 years anniversary !!!!
If you want to learn how to draw a sphingolipid molecule, this is the place to go!
Done in Marseille!
Spectacular vesicles obtained under prebiotic conditions by Juliette Aubé, currently undergradutate student in Biology at Aix-Marseille University (Origin of Life and Molecular Evolution Course): a simple mixture of nonanoic acid, nonanol and water... and that's it!
My 4th PNAS article just published:
Still another ganglioside story!
In this research I did the molecular modeling studies. Here is a sample:
Two other samples (Syt2-GT1b complex):