Succinyl phosphonate

Succinyl phosphonate is a α-Ketoglutarate Dehydrogenase Complex (KGDHC) modulator with neuroprotective activity. Succinyl phosphonate protects this complex, reduces cellular succinyl-CoA concentration, downregulates protein succinylation levels, and inhibits the activity of the α-ketoglutarate dehydrogenase complex. Succinyl phosphonate corrects hypoxic or ethanol-induced behavioral impairments, modulates exploratory behavior and emotional stress responses, and improves hypoxia tolerance. Succinyl phosphonate reduces glutamate excitotoxicity, restores the activity of the α-ketoglutarate dehydrogenase complex, reverses the changes in glutamate dehydrogenase and glutamine synthetase activities induced by β-amyloid (Amyloid-β), modulates cognitive function, and prevents β-amyloid-induced neuronal damage. Succinyl phosphonate improves microglial senescence, alleviates neuroinflammation, reactive oxygen species (ROS) production, lipid peroxidation, and the expression of proinflammatory cytokines. Succinyl phosphonate can be used in the research of Alzheimer's disease, aging-related neuroinflammation, and Parkinson's disease^[1][2][3][4]. In Vitro:Succinyl phosphonate (10 μM; 72 h) reduces succinylation levels and succinyl-CoA concentrations, mitigates LPS (HY-D1056)-induced reactive oxygen species production, lipid accumulation, lipid peroxidation, and pro-inflammatory cytokine expression in BV2 cells and primary mouse microglia, and reduces senescence in VP-16 (HY-13629)-induced aged BV2 cells^[3].
Succinyl phosphonate upregulates active OGDHC quantity in cultured neurons, but this upregulation is impaired by co-treatment with ethanol^[4]. In Vivo:Succinyl phosphonate (intranasal; single dose) pretreatment protects pregnancy-sensitized rats from hypoxia and ethanol-induced behavioral impairment, including normalizing post-hypoxia horizontal moving activity and increasing hypoxia resistance in sensitive animals^[1].
Succinyl phosphonate (10 nM; intra-CA1; 30 minutes after first Aβ_25-35 injection) can block the damaging effects induced by Aβ and neuronal damage, improve the spatial learning and memory abilities of rats, and reverse the decrease in α-KGDHC enzyme activity^[2].
Succinyl phosphonate (1 mg/kg; i.c.v.; single injection) reduces LPS (HY-D1056)-induced hippocampal mitochondrial protein succinylation, including succinylation of SDHA and ECHA, in male C57BL/6J mice^[3].