8208167246

NUCLEUS

DS?

MITOCHONDRIAL

BIOGENESIS

OXIDATIVE

PHOSPHORYLATION

Fig. 3. Targets of epigallocatechin-3-gallate (EGCG), resveratrol (RSV) and hydroxytyrosol (HT) in Down syndromc.

In DS cells(DS highlighted in red)an impairment of complex I (I) and ATP synthase(V)activity occurrcd rcsulting in mitochondrial ATPsynthesisdecrcaseand ROS production incrcasc.

Treatmcnt with EGCG (dark grccn lincs) of DS cells (DS highlighted in grccn) resulted in: (a) stimulation of cAMP/PKA signalling pathway with consequcnt incrcasc of PKA-dcpcndent phosphorylation and activities of complcxcs I and V: (b) scavcnging of intramitochondrial ROS produccd by thc dysfunctional complex I: (c) inhibicion of DRK1A activity with consequent incrcasc of PGC1 -ot cxprcssion: (d) activation of SIRT1 with a consequent PGC1 -a dcacctylation: (c) incrcasc of AMPK phosphorylation and activity with a conscqucnt PCC1-a phosphorylation and activation.

Treatmcnt with RSV (red lincs) resulted in: (a) incrcasc of AMPK phosphorylation and activity with a conscqucnt PGCI-a phosphorylation and activation; (b) activation of SIRT1 with a conscqucnt PGCI-a dcacctylation. In addition RSV. as in other ccii typc. could target mirR-155 (c) and incrcasc cxprcssion of target genes of mitochondrial biogenesis as wcII as target (d) cAMP/PKA signalling pathway with consequent incrcasc of PKA-depcndcnt phosphorylation and activities of complcxcs I and V.

Treatmcnt with HT (light grccn lincs) resulted in: (a) cytoplasmic ROS scavcnging and. as in other ccii typc. could target (b) cAMP/PKA signalling pathway with consequent incrcasc of PKA-dcpcndent phosphorylation and activities of complexes I and V.

Other abbreviations: NM. nuclcar membranę: MOM. mitochondrial outer membranę: IMS. mitochondrial intermembrane spacc: MIM. mitochondrial inner membranę. Respiratory chain complexcs: II. complcx II: Q, cocnzymc Q: III. complcx III: c. cytochromc c: IV. complcx IV.