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P1‐146: PHOSPHOLIPID MEMBRANES PROMOTE THE EARLY STAGE ASSEMBLY OF α‐SYNUCLEIN AGGREGATES
Author(s) -
Zagorski Karen,
Hashemi Mohtadin,
Lv Zhengjian,
Banerjee Siddhartha,
Rochet Chris,
Lyubchenko Yuri L.
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.701
Subject(s) - biophysics , lipid bilayer , chemistry , phospholipid , membrane , protein aggregation , amyloid (mycology) , fibril , phosphatidylserine , bilayer , molecular dynamics , biochemistry , biology , inorganic chemistry , computational chemistry
play an important role in events such as synaptic vesicle release, vesicular traffic and neuron survival. a-synuclein can assist in the assembly of synaptic proteins called SNARE and act as a molecular chaperone in the formation of SNARE complexes, thereby regulating the synaptic vesicle cycle (2). Present study was designed in order to determine the general profile of human SHSY5Y cells which was differentiated into neurons (3,4) in terms of neurotrophic factor synthesis and secretion, and how this profile is altered in response to a-synuclein overexpression.Methods: Human SH-SY5Y cells were differentiated into neuron-like phenotype by retinoic acid treatment. a-synuclein overexpression was performed by human SNCA transfection in differentiated SHSY5Y cells. Levels of 33 released trophic factors and 8 related receptors were detected with Ray Biotech C-Series Human Growth Factor Antibody Array C1 in untreated and a-synuclein overexpressing SH-SY5Y cells. Results: Our results indicated that differentiated human SH-SY5Y cells predominantly secreted insulin related factors and HGF, EGF class, MCSF-R in addition to TGF-b3 and neurotrophic factor NT-4 where they secreted bNGF, G-CSF and EGF-R in lesser amounts and had almost no expression of FGF-4 in optimal culture conditions. a-synuclein overexpression significantly induced IGF-I and SCF-Rs. a-synuclein overexpressing differentiated human SH-SY5Y cells also had increased HB-EGF, TGF-a, TGF-b2 secretion. On the contrary these cells had attenuated levels of IGFBP-2, FGF-6. Conclusions: This is the first study that investigated the general profile of released neurotrophic factors and their receptors in differentiated human SH-SY5Y cells and how this profile is altered by a-synuclein overexpression. The alterations in the key survival molecules by a-synuclein overexpression that we have demonstrated may provide a clue about the initial pathways which will be vulnerable to a-synuclein increment or an initial response in human SH-SY5Y when a-synuclein based pathological processes are on the way.(The present work was supported by the Scientific and Technological Research Council of Turkey-TUBITAK, Project no: 216S887).