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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