Iron Dysregulation and Neurodegeneration: The Molecular Connection

Table 1.

Proteins Involved in Iron Regulation

Protein	Normal Function	Disorder /Dysregulation	Ref
Ferritin	H – ferroxidation  L – iron core formation	Embryonic lethal  Unstable ferritin shells leading to degradation or aggregation	(13)  (15, 16)
IRP-1/2	IRE binding, Fe sensors  Cytoplasmic aconitase (IRP-1)	Aberrant or inappropriate activation of IRE-containing mRNAs; Neurodegeneration with excessive Fe loading with IRP-2 deficiency	(10)  (11)
PANK2	Coenzyme A biosynthesis	Neurodegeneration with Brain Iron Accumulation (NBIA); cysteine buildup triggers Fe-catalyzed oxidative reactions	(33)
HFE	Binds TfR	Hemochromatosis; abnormal interaction between mutated HFE and TfR resulting in iron sequestration	(42)
Frataxin	Heme and Fe-S cluster synthesis  Ferroxidation and mineralization	Friedreich’s ataxia; mitochondrial Fe accumulation	(29)  (32)
Cp	Ferroxidation	Aceruloplasminemia; ↓ Fe export from cells	(19)
HO-1	Heme degradation	↓ iron efflux or ↓ mitochondrial Fe accumulation	(56, 57)
DMT-1	Fe transport into cytosol	Microcytic anemia; ↓ in Fe uptake, ↓ in Fe recirculation	(26)
MTs	Metal binding protein	Disruption of metal homeostasis and redox state	(62, 63)