Producción CyT

Medicina - LIPID DROPLETS AS AN EARLY MARKER OF α-SYNUCLEIN-INDUCED NEURODEGENERATION

Congreso

Autoría:

Alza, Natalia P. ; Conde, Melisa A. ; Scodelaro Bilbao, P ; SALVADOR, GABRIELA ALEJANDRA

Fecha:

2017

Editorial y Lugar de Edición:

TADEO

Resumen *

(447) LIPID DROPLETS AS AN EARLY MARKER OFα-SYNUCLEIN-INDUCED NEURODEGENERATIONNatalia Alza (1), Melisa Conde (2), Paola Scodelaro Bilbao(3), Gabriela Salvador (2)(1) Dpto. Qca.-UNS; INIBIBB-CONICET. (2) Dpto. Biol.,Bioq. y Farm.-UNS; INIBIBB-CONICET. (3) Dpto. Biol., Bioq.y Farm.-UNS; INIBIBB-CONICET, CERZOS-CONICET.Pathological accumulation of α-synuclein (α-syn), a cytosolic proteinhighly expressed in the central nervous system, is a hallmarkof Parkinson?s disease. α-syn has the ability to bind lipids, althoughits involvement in lipid metabolism remains unknown. In previouswork, we reported that the overexpression of A53T α-syn in dopaminergicneurons increased the cellular content of neutral lipids andfatty acids (SAIB 2014-2015). The aim of the present study was tocharacterize the role of α-syn in neuronal lipid metabolism. For thispurpose, we worked with a human neuroblastoma cell line, IMR32,that stably express the wild type form of α-syn (WT α-syn). Weobserved an increase in triacylglycerides (TAG) and cholesterolcontent in WT α-syn neurons when compared with control cells(pcDNA3) (**p<0.01 and ***p<0.001, respectively). In consonancewith these findings, lipid droplets (LD) accumulation in WT α-synneurons was detected. Moreover, the number and the size of LDin the presence of α-syn were increased when LD formation wasinduced by oleic acid (300 y 600 µM). Enhancers of α-syn toxicitysuch as iron, manganese and bortezomib, which increased proteinaggregation, potentiated LD accumulation in WT α-syn neurons. Finally,the pharmacological inhibition of lipins (propranolol) reducedthe viability of WT α-syn neurons with respect to controls (**p<0.01),thus suggesting that the blockage of TAG synthesis turned the neuronsmore vulnerable to the presence of α-syn. Our results allow usto conclude that neurons trigger the accumulation of LD as a neuroprotectivemechanism against α-syn, and that this novel mechanismcould be involved in the determination of neuronal fate. Sponsoredby FONCyT-CONICET-UNS.Keywords: α-synuclein, lipid metabolism, lipid droplets, neurodegeneration.(449) Información suministrada por el agente en SIGEVA

Palabras Clave

NEUROTOXICITYALFA SYNUCLEINLIPID DROPLETSLIPID METABOLISM