The Central Role of Biometals Maintains Oxidative Balance in the Context of Metabolic and Neurodegenerative Disorders

Table 2

Role of reviewed biometals in neurodegenerative diseases.

Biometal	Type of change	Effect	Citation
Fe	Oxidized form (Fe^3+)	(i) Promotes Aβ and α-syn aggregation; (ii) Detected in AD and PD brains	[150, 158, 159, 195]
		↑ intracellular ROS generation	[145, 150, 156–158]
		↑ GSH oxidation	[150, 151]
Cu	Free/unbound	(i) Promotes aggregation of α-syn; ↑ oxidative stress	[160, 162, 163]
	Decrease	↑ of Fe levels	[160]
		(i) Detected in substantia nigra of PD brains	[161]
Zn	Free/unbound	(i) Promotes aggregation of Aβ	[162]
	ATP13A2 deficiency	↑ intracellular free Zn^2+; ↑ ROS production	[161, 167, 168]
Mn	Decrease	(i) LRRK2 G2019S (NOT wt) stays active under ↑ Mn → biological sensor of Mn levels	[171, 178, 179]
	ATP13A2 deficiency	↑ intracellular Mn^2+; ↑ α-syn-induced toxicity	[167, 180, 181, 196]
	Increase	(i) Indirect hyperphosphorylation of tau; (ii) Tau-mediated neuronal death	[183]
Mg	Decrease	(i) High risk factor of PD development; (ii) Regulation of Mg homeostasis; (iii) Protection against protein aggregation	[184–187]
		(iv) Dopamine generation defects	[184]
	Stabilization/slightly increase	(i) Protection against risk of PD development in animal models and humans	[77, 189]

LRRK2 G2019S: mutation type of leucine-rich repeat kinase 2; ATP13A2: probable cation-transporting ATPase 13A2; GSH: glutathione.