A Plant Model of -Synucleinopathy: Expression of -Synuclein A53T Variant in Hairy Root Cultures Leads to Proteostatic Stress and Dysregulation of Iron Metabolism.

Synucleinopathies, typified by Parkinson's disease (PD), entail the accumulation of -synuclein (Syn) aggregates in nerve cells. Various Syn mutants, including the Syn A53T variant linked to early-onset PD, increase the propensity for Syn aggregate formation. In addition to disrupting protein homeostasis and inducing proteostatic stress, the aggregation of Syn in PD is associated with an imbalance in iron metabolism, which increases the generation of reactive oxygen species and causes oxidative stress.

The enantiomer of progesterone (ent-progesterone) is a competitive inhibitor of human cytochromes P450c17 and P450c21.

Human cytochrome P450c17 (17alpha-hydroxylase, 17,20-lyase) (CYP17) and cytochrome P450c21 (21-hydroxylase) (CYP21) differ by only 14 amino acids in length and share 29% amino acid identity. Both enzymes hydroxylate progesterone at carbon atoms that lie only 2.6A apart, but CYP17 also metabolizes other steroids and demonstrates additional catalytic activities.