AmyP53 therapeutic innovation

for Alzheimer and Parkinson

Video explanation of AmyP53 technology.

© Christelle GOBET, a talented student in Neurobiology 

in english:

and in french:

Molecular modeling of amyloid pores (J. Fantini)

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. 

Disruptive technology

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.

Therapeutic implications: 

Reversibility of Aβ oligomer neurotoxicity: Insights into the treatment of Alzheimer’s disease

Our work on the molecular organization of lipid rafts quoted in Wikipedia

(ref. 8 here)

More on lipids here

J. Fantini H-index: 66

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Computational Biology

Molecular basis of Alzheimer and Parkinson diseases

Molecular neuroscience

Small oligomers

Amyloid pores

 Ca2+ imaging

Neurotoxicity

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