dopaminergic cell death

MPP+ iodide, the metabolite of a neurotoxin MPTP, causes symptom of Parkinson's disease (PD) in animal models by selectively destroying dopaminergic neurons in substantia nigra. MPP+ induces dopamine transporter (DAT) externalization in dopaminergic (DA) neurons, but internalization of serotonin transporter (SERT) in serotonergic (5-HT) neurons. MPP+ induces autophagic cell death in SH-SY5Y cells.

AGK7 is an inactive control of AGK2, a selective SIRT2 inhibitor that selectively inhibits SIRT3 over SIRT1 and SIRT2 (IC50 = >5 μM, >50 μM and >50 μM for SIRT3, SIRT1, and SIRT2, respectively).

PAQ is a neuroprotective agent. It protects dopaminergic neurons from cell death without inhibiting glial cell proliferation in a rat midbrain culture model of Parkinson's disease when used at a concentration of 10 μM. PAQ (25 or 50 mg/kg, twice per day) prevents loss of dopaminergic neurons in the substantia nigra in a mouse model of Parkinson's disease induced by MPTP.

Pegsebrenatide (NLY01), a long-acting GLP-1R agonist, exhibits an extended half-life and favorable blood-brain barrier penetration. It impedes A1 astrocyte transformation, mitigates dopaminergic cell death, and ameliorates motor symptoms in mouse models of Parkinson's disease (PD) [1].

The compound 4A7C-301-Nurr1 agonist is a specific agonist for the nuclear receptor-related 1 (Nurr1). By binding to the Nurr1 ligand-binding domain with an IC50 value of 48.22 nM, it enhances the transcriptional activity of both Nurr1-LBD and the full-length Nurr1, as demonstrated in reporter assays using SK-N-BE(2)C human neuroblastoma cells, with EC50 values of 6.53 and 50-70 µM, respectively. Additionally, administration of 4A7C-301-Nurr1 agonist at a dosage of 5 mg/kg per day has been shown to mitigate dopaminergic cell death in the striatum and substantia nigra pars compacta and ameliorate motor and olfactory deficits in mouse models of Parkinson's disease, circumventing the induction of dyskinesia-like behaviors. These models were induced either by the neurotoxin MPTP or by overexpression of α-synuclein.