Evidence map›Paper›PMID 33799121›Full record

ReviewRedox biology2021

Parkinson's disease: Alterations in iron and redox biology as a key to unlock therapeutic strategies.

L Ma, M Gholam Azad, M Dharmasivam, V Richardson, R J Quinn, Y Feng, D L Pountney, K F Tonissen, G D Mellick, I Yanatori and 1 more

Open access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Redox biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 2 pooled it
8.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

72 citing papers in PubMed, 2 syntheses or guidelines pooled it, 137 citations in OpenAlex.

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12 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 2 countries.

L MaSchool of Environment and Science, Griffith University Nathan, Brisbane, Queensland, Australia; Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, Australia.
M Gholam AzadSchool of Environment and Science, Griffith University Nathan, Brisbane, Queensland, Australia; Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, Australia; Centre for Cancer Cell Biology and Drug Discovery, Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, Australia.
M DharmasivamSchool of Environment and Science, Griffith University Nathan, Brisbane, Queensland, Australia; Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, Australia; Centre for Cancer Cell Biology and Drug Discovery, Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, Australia.
V RichardsonSchool of Environment and Science, Griffith University Nathan, Brisbane, Queensland, Australia; Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, Australia; Centre for Cancer Cell Biology and Drug Discovery, Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, Australia.
R J QuinnGriffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, Australia.
Y FengSchool of Environment and Science, Griffith University Nathan, Brisbane, Queensland, Australia; Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, Australia.
D L PountneySchool of Medical Science, Griffith University, Gold Coast, Queensland, Australia.
K F TonissenSchool of Environment and Science, Griffith University Nathan, Brisbane, Queensland, Australia; Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, Australia.
G D MellickSchool of Environment and Science, Griffith University Nathan, Brisbane, Queensland, Australia; Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, Australia.
I YanatoriDepartment of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
D R RichardsonSchool of Environment and Science, Griffith University Nathan, Brisbane, Queensland, Australia; Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, Australia; Centre for Cancer Cell Biology and Drug Discovery, Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, Australia; Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan. Electronic address: d.richardson@griffith.edu.au.
Griffith University · AUNagoya University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A plethora of studies indicate that iron metabolism is dysregulated in Parkinson's disease (PD). The literature reveals well-documented alterations consistent with established dogma, but also intriguing paradoxical observations requiring mechanistic dissection. An important fact is the iron loading in dopaminergic neurons of the substantia nigra pars compacta (SNpc), which are the cells primarily affected in PD. Assessment of these changes reveal increased expression of proteins critical for iron uptake, namely transferrin receptor 1 and the divalent metal transporter 1 (DMT1), and decreased expression of the iron exporter, ferroportin-1 (FPN1). Consistent with this is the activation of iron regulator protein (IRP) RNA-binding activity, which is an important regulator of iron homeostasis, with its activation indicating cytosolic iron deficiency. In fact, IRPs bind to iron-responsive elements (IREs) in the 3ꞌ untranslated region (UTR) of certain mRNAs to stabilize their half-life, while binding to the 5ꞌ UTR prevents translation. Iron loading of dopaminergic neurons in PD may occur through these mechanisms, leading to increased neuronal iron and iron-mediated reactive oxygen species (ROS) generation. The "gold standard" histological marker of PD, Lewy bodies, are mainly composed of α-synuclein, the expression of which is markedly increased in PD. Of note, an atypical IRE exists in the α-synuclein 5ꞌ UTR that may explain its up-regulation by increased iron. This dysregulation could be impacted by the unique autonomous pacemaking of dopaminergic neurons of the SNpc that engages L-type Ca

Indexed as

Parkinson Diseasealpha-SynucleinBiologyHumansIronOxidation-Reductionalpha-SynucleinIronIronNeurodegenerationParkinson's disease

Identifiers

PMID33799121
PMCPMC8044696
OpenAlexW3132583844

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.