INVESTIGADORES
CURINO Alejandro Carlos
congresos y reuniones científicas
Título:
WIRED CHOLESTEROL METABOLISM IS RELATED WITH FERROPTOSIS LEADING TO PARKINSONISM-LIKE DISORDERS
Autor/es:
MANISCALCHI A.; BENZI JUNCOS O.N.; CONDE M.C.; FERMENTO M.E.; FUNK M.I.; CURINO A. C.; FACCHINETTI M.M.; ALZA N.P.; SALVADOR G.A.
Lugar:
Mar del Plata
Reunión:
Congreso; Reunión Anual de Sociedades de Biociencias. LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2022
Institución organizadora:
Sociedad Argentina de Investigación Clínica (SAIC).
Resumen:
Ferroptosis is a novel type of oxidative and non-apoptotic cell death associated with neurodegenerative disorders. Previously, we have established an in vivo model of iron overload (C57BL/6 mice treated with iron-sucrose) that triggers ferroptosis in the nervous system related with markers of neurodegeneration. Our aim was to characterize lipid metabolism alterations in mice midbrain of this experimental model. We found that midbrain lipid content was altered by iron overload. Cholesterol and diacylglycerol levels were increased, while their acylated forms diminished. Neutral lipid changes were associated with elevated hydrolysis catalyzed by mono- di- and triacylglycerol lipases. A reduced activity of acylation enzymes, such as acyl-CoA, lysophospholipid and monoacylglycerol acyltransferases was also observed. Furthermore, SREBP-1 and filipin staining was increased by iron treatment. Besides motor skill impairment, iron-treated mice presented a decreased recognition memory. To ascertain the role of neuronal-glia communication in cholesterol metabolism, we exposed N27 dopaminergic neurons and C6 astrocytes to iron -overload. Astrocytes showed the highest levels of cholesterol accumulation upon treatment. Our findings indicate that impaired cholesterol and triacylglycerol metabolism are biomarkers of midbrain neurodegeneration triggered by ferroptosis.