Ferroptosis as a New Mechanism in Parkinson’s Disease Therapy Using Traditional Chinese Medicine

Abstract

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. To date, among medications used to treat PD, only levodopa exhibits a limited disease-modifying effect on early-onset PD, but it cannot delay the progression of the disease. In 2018, for the first time, the World Health Organization included traditional Chinese medicine (TCM) in its influential global medical compendium. The use of TCM in the treatment of PD has a long history. At present, TCM can help treat and prevent PD. Iron metabolism is closely associated with PD. Ferroptosis, which is characterized by the accumulation of lipid peroxides, is a recently discovered form of iron-dependent cell death. The research literature indicates that ferroptosis in dopaminergic neurons is an important pathogenetic mechanism of PD. TCM may thus play unique roles in the treatment of PD and provide new ideas for the treatment of PD by regulating pathways associated with ferroptosis.

Oxidative Stress and Mitochondrial Complex I Dysfunction Correlate with Neurodegeneration in an α-Synucleinopathy Animal Model

“…On the other hand, LP mediated by iron and reduced glutathione (GSH) depletion leads to a cell death pathway defined as ferroptosis, which may also occur in PD [ 49 , 50 ]. Future experiments are required to determine if the BSSG model exhibits this death mechanism.…”

Modified Iron Deposition in Nigrosomes by Pharmacotherapy for the Management of Parkinson’s Disease

“…The levodopa molecule is known to contain a domain with iron-chelating properties or the ability to prevent iron deposition and the toxic effects of extra free iron ( Billings et al, 2019 ; Alhassen et al, 2022 ). Iron transport is regulated by the hepcidin–ferroportin system to control iron release into the plasma ( Wu et al, 2021 ). Hepcidin expression is principally regulated by plasma iron in a feedback loop ( Zucca et al, 2017 ).…”

Recent advances in small-molecule fluorescent probes for studying ferroptosis

“…72 Iron has been shown to regulate ferroptosis pathway through at least by three mechanisms: (1) iron is a key component of various metabolic enzymes and energy-generating protein complexes, which generates cellular ROS through oxidation-based metabolic processes, (2) iron is regarded as a cofactor of LOX and cytochrome P450 oxidoreductase (POR) which are crucial in the generation of phospholipid peroxides, and (3) Iron promotes LPO by catalyzing Fenton reaction or Haber-Weiss reaction to produce lipid ROS. 73,74 Moreover, LPO is initiated by which oxidants (e.g., free radicals or non-free radical substances) attack the carbon-carbon double bonds of lipids (especially in polyunsaturated fatty acids (PUFAs)) to form oxidized lipid membranes via non-enzymatic Fenton reaction or enzymatic reaction pathways. 75 Eventually, this process results in membrane destruction and cell death.…”

“…Iron-containing heme oxygenase-1 (HO-1), a critical enzyme in heme metabolism, can decompose heme into Fe 2+ and biliverdin. 73 On the one hand, elevated HO-1 can induce ferroptosis through increasing the LIP upon metabolizing heme. [163][164][165] In particular, ferroptosis induced by excessive HO-1 activity is called non-canonical ferroptosis.…”