Iron Dysregulation in Parkinson's Disease: Focused on the Autophagy-Lysosome Pathway.


:Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic neuron loss in the substantia nigra pars compacta (SNpc). Although both iron accumulation and a defective autophagy-lysosome pathway contribute to the pathological development of PD, the connection between these two causes is poorly documented. The autophagy-lysosome pathway not only responds to regulation by iron chelators and channels but also participates in cellular iron recycling through the degradation of ferritin and other iron-containing components. Previously, ferritin has been posited to be the bridge between iron accumulation and autophagy impairment in PD. In addition, iron directly interacts with α-synuclein in Lewy bodies, which are primarily digested through the autophagy-lysosome pathway. These findings indicate that some link exists between iron deposition and autophagy impairment in PD. In this review, the basic mechanisms of the autophagy-lysosome pathway and iron trafficking are introduced, and then their interaction under physiological conditions is explained. Finally, we finish by discussing the dysfunction of iron deposition and autophagy in PD, as well as their potential relationship, which will provide some insight for further study.


ACS Chem Neurosci


Chen LL,Huang YJ,Cui JT,Song N,Xie J




Has Abstract


2019-02-20 00:00:00










  • Serotonin: A New Hope in Alzheimer's Disease?

    abstract::Alzheimer's disease (AD) is the most common form of dementia affecting 35 million individuals worldwide. Current AD treatments provide only brief symptomatic relief. It is therefore urgent to replace this symptomatic approach with a curative one. Increasing serotonin signaling as well as developing molecules that enha...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Claeysen S,Bockaert J,Giannoni P

    更新日期:2015-07-15 00:00:00

  • Novel Disassembly Mechanisms of Sigmoid Aβ42 Protofibrils by Introduced Neutral and Charged Drug Molecules.

    abstract::Alzheimer's disease (AD) is characterized by fibrillar deposits of amyloid-β (Aβ) peptides and neurofibrillary tangles of Tau proteins. Aβ peptides are composed of 37-49 residues, among which the Aβ42 isoform is particularly toxic and aggregation-prone and is enriched in the plaques of AD brains and thus considered ce...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Xing X,Liu C,Ali A,Kang B,Li P,Ai H

    更新日期:2020-01-02 00:00:00

  • Akt-dependent and isoform-specific regulation of dopamine transporter cell surface expression.

    abstract::Dopamine (DA) is a neurotransmitter implicated in multiple functions, including movement, cognition, motivation, and reward. The DA transporter (DAT) is responsible for clearing extracellular DA, thereby terminating DA neurotransmission. Previously, it has been shown that insulin signaling through protein kinase B/Akt...

    journal_title:ACS chemical neuroscience

    pub_type: 信件


    authors: Speed NK,Matthies HJ,Kennedy JP,Vaughan RA,Javitch JA,Russo SJ,Lindsley CW,Niswender K,Galli A

    更新日期:2010-07-21 00:00:00

  • A small linear peptide encompassing the NGF N-terminus partly mimics the biological activities of the entire neurotrophin in PC12 cells.

    abstract::Ever since the discovery of its neurite growth promoting activity in sympathetic and sensory ganglia, nerve growth factor (NGF) became the prototype of the large family of neurotrophins. The use of primary cultures and clonal cell lines has revealed several distinct actions of NGF and other neurotrophins. Among severa...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Travaglia A,Pietropaolo A,Di Martino R,Nicoletti VG,La Mendola D,Calissano P,Rizzarelli E

    更新日期:2015-08-19 00:00:00

  • Intranasally Administered S100A9 Amyloids Induced Cellular Stress, Amyloid Seeding, and Behavioral Impairment in Aged Mice.

    abstract::Amyloid formation and neuroinflammation are major features of Alzheimer's disease pathology. Proinflammatory mediator S100A9 was shown to act as a link between the amyloid and neuroinflammatory cascades in Alzheimer's disease, leading together with Aβ to plaque formation, neuronal loss and memory impairment. In order ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Iashchishyn IA,Gruden MA,Moskalenko RA,Davydova TV,Wang C,Sewell RDE,Morozova-Roche LA

    更新日期:2018-06-20 00:00:00

  • Microscopic visualization of metabotropic glutamate receptors on the surface of living cells using bifunctional magnetic resonance imaging probes.

    abstract::A series of bimodal metabotropic glutamate-receptor targeted MRI contrast agents has been developed and evaluated, based on established competitive metabotropic Glu receptor subtype 5 (mGluR5) antagonists. In order to directly visualize mGluR5 binding of these agents on the surface of live astrocytes, variations in th...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Mishra A,Mishra R,Gottschalk S,Pal R,Sim N,Engelmann J,Goldberg M,Parker D

    更新日期:2014-02-19 00:00:00

  • A Review of Single-Nucleotide Polymorphisms in Orexigenic Neuropeptides Targeting G Protein-Coupled Receptors.

    abstract::Many physiological pathways are involved in appetite, food intake, and the maintenance of energy homeostasis. In particular, neuropeptides within the central nervous system have been demonstrated to be critical signaling molecules for modulating appetite. Both anorexigenic (appetite-decreasing) and orexigenic (appetit...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审


    authors: Ericson MD,Haskell-Luevano C

    更新日期:2018-06-20 00:00:00

  • Structure-selective anisotropy assay for amyloid Beta oligomers.

    abstract::Amyloid β (Abeta) peptides in their oligomeric form have been proposed as major toxic species in Alzheimer's disease (AD). There are a limited number of anti-Abeta antibodies specific to oligomeric forms of Abeta compared to the monomeric form, and accurate measurement of oligomeric forms in biological samples, cerebr...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Matveeva EG,Rudolph A,Moll JR,Thompson RB

    更新日期:2012-11-21 00:00:00

  • Autoimmune Attack of the Neuromuscular Junction in Myasthenia Gravis: Nicotinic Acetylcholine Receptors and Other Targets.

    abstract::The nicotinic acetylcholine receptor (nAChR) family, the archetype member of the pentameric ligand-gated ion channels, is ubiquitously distributed in the central and peripheral nervous systems, and its members are the targets for both genetic and acquired forms of neurological disorders. In the central nervous system,...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审


    authors: Paz ML,Barrantes FJ

    更新日期:2019-05-15 00:00:00

  • Structure-activity relationships in peptide modulators of β-amyloid protein aggregation: variation in α,α-disubstitution results in altered aggregate size and morphology.

    abstract::Neuronal cytotoxicity observed in Alzheimer's disease (AD) is linked to the aggregation of β-amyloid peptide (Aβ) into toxic forms. Increasing evidence points to oligomeric materials as the neurotoxic species, not Aβ fibrils; disruption or inhibition of Aβ self-assembly into oligomeric or fibrillar forms remains a via...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Bett CK,Ngunjiri JN,Serem WK,Fontenot KR,Hammer RP,McCarley RL,Garno JC

    更新日期:2010-09-15 00:00:00

  • Amyloid-β Peptide Targeting Peptidomimetics for Prevention of Neurotoxicity.

    abstract::A new generation of ligands designed to interact with the α-helix/β-strand discordant region of the amyloid-β peptide (Aβ) and to counteract its oligomerization is presented. These ligands are designed to interact with and stabilize the Aβ central helix (residues 13-26) in an α-helical conformation with increased inte...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Honcharenko D,Juneja A,Roshan F,Maity J,Galán-Acosta L,Biverstål H,Hjorth E,Johansson J,Fisahn A,Nilsson L,Strömberg R

    更新日期:2019-03-20 00:00:00

  • 5-HT2B, 5-HT7, and DA2 Receptors Mediate the Effects of 5-HT and DA on Agonistic Behavior of the Chinese Mitten Crab (Eriocheir sinensis).

    abstract::The Chinese mitten crab (Eriocheir sinensis) is a commercially important crab in China and is usually managed at high stocking densities. Agonistic behavior directly impacts crab integrity, survival, and growth and results in economic losses. In the present study, we evaluated the modulatory effects of serotonin (5-HT...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Pang YY,Song YM,Zhang L,Song XZ,Zhang C,Lv JH,He L,Cheng YX,Yang XZ

    更新日期:2019-11-20 00:00:00

  • Synergism between a serotonin 5-HT2A receptor (5-HT2AR) antagonist and 5-HT2CR agonist suggests new pharmacotherapeutics for cocaine addiction.

    abstract::Relapse to cocaine dependence, even after extended abstinence, involves a number of liability factors including impulsivity (predisposition toward rapid, unplanned reactions to stimuli without regard to negative consequences) and cue reactivity (sensitivity to cues associated with cocaine-taking which can promote coca...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Cunningham KA,Anastasio NC,Fox RG,Stutz SJ,Bubar MJ,Swinford SE,Watson CS,Gilbertson SR,Rice KC,Rosenzweig-Lipson S,Moeller FG

    更新日期:2013-01-16 00:00:00

  • Tautomerization Effect of Histidines on Oligomer Aggregation of β-Amyloid(1-40/42) during the Early Stage: Tautomerism Hypothesis for Misfolding Protein Aggregation.

    abstract::As the intrinsic origin of the hypothesis for β-amyloid (Aβ) from Alzheimer's disease, histidine behaviors were found to play a crucial role in Aβ aggregation. To investigate the histidine behaviors during the early stage of aggregation, Aβ40/42 pentamers with different histidine isomer states were simulated at the at...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Xing X,Zhao W,Hu D,Kang B,Shi H,Lee JY,Ai H

    更新日期:2019-05-15 00:00:00

  • The implications of angiotensin-converting enzymes and their modulators in neurodegenerative disorders: current and future perspectives.

    abstract::Angiotensin converting enzyme (ACE) is a dipeptidyl peptidase transmembrane bound enzyme. Generally, ACE inhibitors are used for the cardiovascular disorders. ACE inhibitors are primary agents for the management of hypertension, so these cannot be avoided for further use. The present Review focuses on the implications...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审


    authors: Kaur P,Muthuraman A,Kaur M

    更新日期:2015-04-15 00:00:00

  • In Utero Exposure to Citalopram Mitigates Maternal Stress Effects on Fetal Brain Development.

    abstract::Human epidemiological and animal-model studies suggest that separate exposure to stress or serotonin-selective reuptake inhibitor (SSRI) antidepressants during pregnancy increases risks for neurodevelopmental disorders in offspring. Yet, little is known about the combined effects of maternal stress and SSRIs with rega...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Velasquez JC,Zhao Q,Chan Y,Galindo LCM,Simasotchi C,Wu D,Hou Z,Herod SM,Oberlander TF,Gil S,Fournier T,Burd I,Andrews AM,Bonnin A

    更新日期:2019-07-17 00:00:00

  • Increased Brain Exposure of an Alpha-Synuclein Fibrillization Modulator by Utilization of an Activated Ester Prodrug Strategy.

    abstract::Previous work in our laboratories has identified a series of peptidomimetic 2-pyridone molecules as modulators of alpha-synuclein (α-syn) fibrillization in vitro. As a first step toward developing molecules from this scaffold as positron emission tomography imaging agents, we were interested in evaluating their blood-...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Cairns AG,Vazquez-Romero A,Mahdi Moein M,Ådén J,Elmore CS,Takano A,Arakawa R,Varrone A,Almqvist F,Schou M

    更新日期:2018-11-21 00:00:00

  • Comparison of the binding and functional properties of two structurally different D2 dopamine receptor subtype selective compounds.

    abstract::We previously reported on the synthesis of substituted phenyl-4-hydroxy-1-piperidyl indole analogues with nanomolar affinity at D2 dopamine receptors, ranging from 10- to 100-fold selective for D2 compared to the D3 dopamine receptor subtype. More recently, we evaluated a panel of aripiprazole analogues, identifying s...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Luedtke RR,Mishra Y,Wang Q,Griffin SA,Bell-Horner C,Taylor M,Vangveravong S,Dillon GH,Huang RQ,Reichert DE,Mach RH

    更新日期:2012-12-19 00:00:00

  • Glycerolipid Headgroups Control Rate and Mechanism of Superoxide Dismutase-1 Aggregation and Accelerate Fibrillization of Slowly Aggregating Amyotrophic Lateral Sclerosis Mutants.

    abstract::Interactions between superoxide dismutase-1 (SOD1) and lipid membranes might be directly involved in the toxicity and intercellular propagation of aggregated SOD1 in amyotrophic lateral sclerosis (ALS), but the chemical details of lipid-SOD1 interactions and their effects on SOD1 aggregation remain unclear. This paper...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Rasouli S,Abdolvahabi A,Croom CM,Plewman DL,Shi Y,Shaw BF

    更新日期:2018-07-18 00:00:00

  • Immunochemical Detection of α-Synuclein Autoantibodies in Parkinson's Disease: Correlation between Plasma and Cerebrospinal Fluid Levels.

    abstract::Autoantibodies to Parkinson's disease (PD) amyloidogenic protein, α-synuclein, were recognized as a prospective biomarker for early disease diagnostics, yet there is inconsistency in previous reports, potentially related to PD status. Therefore, plasma and cerebrospinal fluid (CSF) of the cross-sectional cohort of 60 ...

    journal_title:ACS chemical neuroscience

    pub_type: 信件


    authors: Horvath I,Iashchishyn IA,Forsgren L,Morozova-Roche LA

    更新日期:2017-06-21 00:00:00

  • An azobenzene photoswitch sheds light on turn nucleation in amyloid-β self-assembly.

    abstract::Amyloid-β (Aβ) self-assembly into cross-β amyloid fibrils is implicated in a causative role in Alzheimer's disease pathology. Uncertainties persist regarding the mechanisms of amyloid self-assembly and the role of metastable prefibrillar aggregates. Aβ fibrils feature a sheet-turn-sheet motif in the constituent β-stra...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Doran TM,Anderson EA,Latchney SE,Opanashuk LA,Nilsson BL

    更新日期:2012-03-21 00:00:00

  • High affinity radiopharmaceuticals based upon lansoprazole for PET imaging of aggregated tau in Alzheimer's disease and progressive supranuclear palsy: synthesis, preclinical evaluation, and lead selection.

    abstract::Abnormally aggregated tau is the hallmark pathology of tauopathy neurodegenerative disorders and is a target for development of both diagnostic tools and therapeutic strategies across the tauopathy disease spectrum. Development of carbon-11- or fluorine-18-labeled radiotracers with appropriate affinity and specificity...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Fawaz MV,Brooks AF,Rodnick ME,Carpenter GM,Shao X,Desmond TJ,Sherman P,Quesada CA,Hockley BG,Kilbourn MR,Albin RL,Frey KA,Scott PJ

    更新日期:2014-08-20 00:00:00

  • Positive Allosteric Modulation of the 5-HT1A Receptor by Indole-Based Synthetic Cannabinoids Abused by Humans.

    abstract::The nonmedical (i.e., recreational) misuse of synthetic cannabinoids (SCs) is a worldwide public health problem. When compared to cannabis, the misuse of SCs is associated with a higher incidence of serious adverse effects, suggesting the possible involvement of noncannabinoid sites of action. Here, we find that, unli...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Yano H,Adhikari P,Naing S,Hoffman AF,Baumann MH,Lupica CR,Shi L

    更新日期:2020-05-20 00:00:00

  • Characterization and first human investigation of FIBT, a novel fluorinated Aβ plaque neuroimaging PET radioligand.

    abstract::Imidazo[2,1-b]benzothiazoles (IBTs) are a promising novel class of amyloid positron emission tomography (PET) radiopharmaceuticals for diagnosis of neurodegenerative disorders like Alzheimer's disease (AD). Their good in vivo imaging properties have previously been shown in preclinical studies. Among IBTs, fluorinated...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Yousefi BH,Manook A,Grimmer T,Arzberger T,von Reutern B,Henriksen G,Drzezga A,Förster S,Schwaiger M,Wester HJ

    更新日期:2015-03-18 00:00:00

  • Investigation of a calcium-responsive contrast agent in cellular model systems: feasibility for use as a smart molecular probe in functional MRI.

    abstract::Responsive or smart contrast agents (SCAs) represent a promising direction for development of novel functional MRI (fMRI) methods for the eventual noninvasive assessment of brain function. In particular, SCAs that respond to Ca(2+) may allow tracking neuronal activity independent of brain vasculature, thus avoiding th...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Angelovski G,Gottschalk S,Milošević M,Engelmann J,Hagberg GE,Kadjane P,Andjus P,Logothetis NK

    更新日期:2014-05-21 00:00:00

  • Maternal Exposure to Di-(2-ethylhexyl) Phthalate Impairs Hippocampal Synaptic Plasticity in Male Offspring: Involvement of Damage to Dendritic Spine Development.

    abstract::Exposure to di-(2-ethylhexyl) phthalate (DEHP), a widely used kind of plasticizer, can result in neurodevelopment impairments and learning and memory disorders. We studied the effects and possible mechanisms of maternal DEHP treatment on hippocampal synaptic plasticity in offspring. Pregnant Wistar rats were randomly ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Dong J,Fu H,Fu Y,You M,Li X,Wang C,Leng K,Wang Y,Chen J

    更新日期:2021-01-20 00:00:00

  • Discovery of a new class of ionotropic glutamate receptor antagonists by the rational design of (2S,3R)-3-(3-carboxyphenyl)-pyrrolidine-2-carboxylic acid.

    abstract::The kainic acid (KA) receptors belong to the class of glutamate (Glu) receptors in the brain and constitute a promising target for the treatment of neurological and/or psychiatric diseases such as schizophrenia, major depression, and epilepsy. Five KA subtypes have been identified and named GluK1-5. In this article, w...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Larsen AM,Venskutonytė R,Valadés EA,Nielsen B,Pickering DS,Bunch L

    更新日期:2011-02-16 00:00:00

  • Eckmaxol, a Phlorotannin Extracted from Ecklonia maxima, Produces Anti-β-amyloid Oligomer Neuroprotective Effects Possibly via Directly Acting on Glycogen Synthase Kinase 3β.

    abstract::Alzheimer's disease is a progressive neurodegenerative disorder that mainly affects the elderly. Soluble β-amyloid oligomer, which can induce neurotoxicity, is generally regarded as the main neurotoxin in Alzheimer's disease. Here we report that eckmaxol, a phlorotannin extracted from the brown alga Ecklonia maxima, c...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Wang J,Zheng J,Huang C,Zhao J,Lin J,Zhou X,Naman CB,Wang N,Gerwick WH,Wang Q,Yan X,Cui W,He S

    更新日期:2018-06-20 00:00:00

  • Real-Time Monitoring of Alzheimer's-Related Amyloid Aggregation via Probe Enhancement-Fluorescence Correlation Spectroscopy.

    abstract::This work describes the use of fluorescence correlation spectroscopy (FCS) and a novel amyloid-binding fluorescent probe, ARCAM 1, to monitor the aggregation of the Alzheimer's disease-associated amyloid β-peptide (Aβ). ARCAM 1 exhibits a large increase in fluorescence emission upon binding to Aβ assemblies, making it...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Guan Y,Cao KJ,Cantlon A,Elbel K,Theodorakis EA,Walsh DM,Yang J,Shah JV

    更新日期:2015-09-16 00:00:00

  • Ethanol Induced Brain Lipid Changes in Mice Assessed by Mass Spectrometry.

    abstract::Alcohol abuse is a chronic disease characterized by the consumption of alcohol at a level that interferes with physical and mental health and causes serious and persistent changes in the brain. Lipid metabolism is of particular interest due to its high concentration in the brain. Lipids are the main component of cell ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Roux A,Jackson SN,Muller L,Barbacci D,O'Rourke J,Thanos PK,Volkow ND,Balaban C,Schultz JA,Woods AS

    更新日期:2016-08-17 00:00:00