Chemically Induced Models of Parkinson’s Disease: History and Perspectives for the Involvement of Ferroptosis

Abstract

Ferroptosis is a newly discovered form of necrotic cell death characterized by its dependency on iron and lipid peroxidation. Ferroptosis has attracted much attention recently in the area of neurodegeneration since the involvement of ferroptosis in Parkinson’s disease (PD), a major neurodegenerative disease, has been indicated using animal models. Although PD is associated with both genetic and environmental factors, sporadic forms of PD account for more than 90% of total PD. Following the importance of environmental factors, various neurotoxins are used as chemical inducers of PD both in vivo and in vitro. In contrast to other neurodegenerative diseases such as Alzheimer’s and Huntington’s diseases (AD and HD), many of the characteristics of PD can be reproduced in vivo by the use of specific neurotoxins. Given the indication of ferroptosis in PD pathology, several studies have been conducted to examine whether ferroptosis plays role in the loss of dopaminergic neurons in PD. However, there are still few reports showing an authentic form of ferroptosis in neuronal cells during exposure to the neurotoxins used as PD inducers. In this review article, we summarize the history of the uses of chemicals to create PD models in vivo and in vitro. Besides, we also survey recent reports examining the possible involvement of ferroptosis in chemical models of PD.

Ferroptosis: A New Regulatory Mechanism in Osteoporosis

“…Iron, an essential trace element for humans and a necessary substance for life, plays a vital role in many biochemical processes, including oxygen transport, enzymatic reactions, and immune reactions. With accumulating research, various physiological and pathological processes, such as tumor, Parkinson's disease, atherosclerosis, viral infection, osteoporosis, immune response, and ischemia-reperfusion injury, have been found to be related to ferroptosis [6][7][8], and ferroptosis is expected to become a new research direction for disease treatment.…”

Liposomes loaded with polyphenol-rich grape pomace extracts protect from neurodegeneration in a rotenone-basedin vitromodel of Parkinson's disease

“…Rotenone is an inhibitor of the mitochondrial electron transport chain complex I commonly used to induce PD-like features both in vivo and in vitro. [39][40][41] In particular, we assessed the ability of ext-LSs to reduce ROS, to improve cell viability, and to hinder α-syn aggregation in the in vitro PD model.…”

The use of phosphorescence oxygen analyzer to measure the effects of rotenone and 1-methyl-4-phenylpyridinium on striatal cellular respiration in C57BL6 mice

“…The potential link between Parkinson's disease and mitochondrial poisons, such as rotenone and MPTP has been extensively studied [ 5 , 6 ]. These mitochondrial toxins can alter the cellular bioenergetics of the midbrain, causing substantial changes in the dopaminergic neurons [ 7 ]. In this study, we used these two respiratory inhibitors to measure their direct effects on striatal oxygen consumption.…”

“…Our hypothesis here is that cellular respiration is a useful biomarker for studying the adverse effects of neurotoxins on the striatum. The main aim of this study is to use the phosphorescence oxygen analyzer to measure striatal cellular respiration in the presence and absence of neurotoxins that are known to cause symptoms similar to Parkinson's disease [ 7 , 8 , 9 ].…”