TABLE 2.

Pathological changes of NDDs associated with pathological features of ferroptosis.

Diseases	Ferroptosis-related Pathological Features	Potential pathological outcome	References
AD	Abnormal iron metabolism and iron deposition	Accumulation and aggregation of Aβ and Tau proteins	Ayton et al., 2020; Derry et al., 2020
		Abnormal increase in APP level and tau hyperphosphorylation and aggregation;	Altamura and Muckenthaler, 2009; McIntosh et al., 2019; Derry et al., 2020
		Microglial activation and neuroinflammation	van Duijn et al., 2017; McIntosh et al., 2019
		Neuronal death and NFT deterioration	Wan et al., 2019
	Redox imbalance and oxidative stress	Abnormal increase of Aβ oligomer and neuroinflammation	Saito et al., 2019
	Decreased GPX4 protein levels and elevated lipid peroxidation products	Hippocampal neurodegeneration	Hambright et al., 2017
PD	Oxidative distress and lipid peroxidation	Degeneration and loss of dopaminergic neurons	Dias et al., 2013; Hare and Double, 2016; Dionísio et al., 2021
	Abnormal iron metabolism and lipid peroxidation	α-synuclein aggregation	Angelova et al., 2020; Riederer et al., 2021
	Increased iron in SN	Aggregation and dopaminergic neuron death	Wang et al., 2009; Zhu et al., 2017; Zhang Y. et al., 2020
	Decreased GPX4 in SN	Dopaminergic neuron axon damage	Bellinger et al., 2011
	Decrease FPN expression	Microglia proinflammatory transformation	Zhang et al., 2014
	Iron homeostasis and iron deposition	Microglia activation and dopaminergic cell death	Wang Z. L. et al., 2022
	Down-regulation of the SLC7A11 gene and decreased SLC7A11 protein level	Neuroinflammation	Vallerga et al., 2020
	Elevated lipid peroxidation products and decreased GSH protein level	Increased Lewy bodies	Jenner et al., 1992
	DJ-1 gene mutation	Decreased GPX4 and GSH activity	Cao et al., 2020
HD	Iron overload and increased lipid peroxidation	Mitochondrial dysfunction and oxidative distress damage	Agrawal et al., 2018
	Decreased GPX4 activity	HTTP gene variants	Mason et al., 2013
	Recurrent glutamate abnormalities	Mitochondrial dysfunction	Reddy and Shirendeb, 2012
ALS	GPX4 depletion	Loss of motor neurons	Evans et al., 2022
	Changes in iron metabolizing proteins and elevated iron levels	SOD1 gene mutations	Jeong et al., 2009
	GSH/GPX4 depletion and increased lipid peroxidation	SOD1 gene mutations	Wang et al., 2021; Peng et al., 2022
MS	Decreased GSH protein level and systemXc– activity	Microglial activation and neuroinflammation	Hu et al., 2019
	Glutathione deficiency and lipid peroxidation	Oligodendrocyte loss and demyelination	Jhelum et al., 2020