Periodic Reporting for period 1 - toxiclipasyn (Understanding the balance between functional and deleterious interactions of alpha-synuclein with lipid bilayers)
Período documentado: 2017-05-01 hasta 2019-04-30
PD is characterized by the deposition of protein clumps called Lewy Bodies (LB) and Lewy neurites (LN) in the brain of patients. LB and LN are mainly composed of the protein alpha-synuclein but can also contain lipid (fat) molecules, the main constituents of biological membrane. A-synuclein interacts with membranes as part of its functional role, i.e. to help neurons to communicate with one another, but alpha-synuclein also form clumps in their presence. Indeed, the nature of lipids in membrane dictates whether or not alpha-synuclein is functional or can form clumps.
This action aimed at identifying changes in lipid levels and/ or properties associated with PD and determining their influence on the propensity of alpha-synuclein to form clumps.
The aims of this action were overall successfully addressed.
The results of this action allowed the identification of a list of lipids whose levels and properties affect alpha-synuclein aggregation under pathophysiologically relevant conditions. In particular, data support the concept that PD risk factors may act by changing cellular lipid profiles and thus promoting the formation of alpha-synuclein clumps.
These results are currently described in a manuscript in preparation for publication. Once published, these results will be presented in conferences targeted at scientists in the field of neuroscience, lipid metabolism and protein aggregation.