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Table 2 Role of hepcidin in brain diseases

From: Hepcidin, an emerging and important player in brain iron homeostasis

Methods Brain disease Main results References
Expression measured with RT-PCR, while protein levels were measured with western blotting and immunohistochemistry (rat and mice brain samples) Focal brain ischemia/reperfusion model Hepcidin↑ in brain tissue
Knock-down of hepcidin with siRNA causes FPN↑ and ferritin↓
Ding et al. [52]
Levels of protein measured with western blotting and ELISA (mice brain samples) Intracerebral hemorrhage (ICH) model Brain and serum hepcidin↑
Hepc−/− mice are protected from brain damage during ICH
Injection of hepcidin increases brain damage
Increased hepcidin inhibits BMVEC iron efflux
The source of brain hepcidin are astrocytes
Brain hepcidin upregulation is induced due to activation of TLR4 pathway
Cellular iron-load is reduced by antagonizing local hepcidin
Xiong et al. [18]
Protein levels measured with western blotting and immunohistochemistry (rat brain samples) Subarachnoid hemorrhage model Hepcidin↑
Hepcidin injections increase brain damage
Hepcidin knock-down with siRNA decreases apoptosis and brain damage
Tan et al. [119]
Serum protein levels measured with ELISA in 86 patients ICH Hepcidin↑
Higher hepcidin is associated with poorer outcome
Hepcidin correlates with inflammatory markers
Serum hepcidin is independently associated with mRS scorea
Xiong et al. [114]
Serum protein levels measured with ELISA in 60 children Acute ischemic stroke (AIS) Hepcidin↑
Hepcidin is correlated with inflammatory markers
Azab et al. [111]
Serum protein levels measured with ELISA in 74 patients Ischemic stroke Hepcidin↑
Hepcidin is correlated with inflammatory markers
Petrova et al. [113]
Serum protein levels measured with ELISA in 31 patients AIS Hepcidin↑ Slomka et al. [112]
Protein levels measured with western blotting and immunohistochemistry in brain samples of humans and transgenic mice Alzheimers disease (AD) Hepcidin↓ in human samples
Hepcidin↓ in mice samples in advanced stages of the disease
Hepcidin staining is associated with hem-rich deposits
Hepcidin distribution is observed in surviving neurons around amyloid plaques
Raha et al. [35]
Serum protein levels measured with ELISA in 52 patients AD Hepcidin↑
Serum hepcidin correlates with CDR-SOBb
Sternberg et al. [89]
Expression measured with RT-PCR and protein levels measured with western blotting and immunohistochemistry (neuronal cell cultures) Parkinson disease model induced by 6-OHDA Hepcidin mRNA↑
EGCG attenuates brain damage by reducing hepcidin expression
Chen et al. [94]
Expression measured with RT-PCR (neuronal cell cultures) Parkinson disease model induced by 6-OHDA Hepcidin knock-down offers protection from 6-OHDA neurotoxicity Xu et al. [95]
Expression measured with RT-PCR (human brain samples) Brain tumors Hepcidin mRNA↓ in most tumor samples Hänninen et al. [69]
Serum protein levels measured with ELISA method in rats Amyotrophic lateral sclerosis Hepcidin↑ Halon et al. [134]
Protein levels measured with immunoblotting, ELISA and immunohistochemistry in 39 patients Restless leg syndrome (RLS) Prohepcidin↑ in brain tissue
Prohepcidin↓ in cerebrospinal fluid in early-onset disease
Clardy et al. [140]
Expression measured with RT-PCR in rat brains Chronic mild stress Hepcidin mRNA↑
Dalteparin lowers hepcidin expression
Hepcidin expression is associated with cellular iron-overload and IL-6 expression
Farajdokht et al. [156]
  1. 6-OHDA 6-hydroxydopamine, BMVEC brain microvascular endothelial cells, EGCG epigallocatechin gallate, ELISA enzyme-linked immunosorbent assay, FPN ferroportin, IL- 6 interleukin 6, RT-PCR reverse transcription polymerase chain reaction, siRNA small interfering RNA, TLR4 toll-like receptor 4
  2. amRS score: modified Rankin Scale measures the degree of disability in patients who have suffered a stroke
  3. bCDR-SOB: Clinical Dementia Rating Scale Sum of Boxes is used to quantify the severity of dementia