Multi-Target Neuroprotection of Thiazolidinediones on Alzheimer’s Disease via Neuroinflammation and Ferroptosis

Safety and efficacy of leriglitazone for preventing disease progression in men with adrenomyeloneuropathy (ADVANCE): a randomised, double-blind, multi-centre, placebo-controlled phase 2–3 trial

(2023) Wolfgang Köhler et al.   LANCET NEUROLOGY

Enhanced defense against ferroptosis ameliorates cognitive impairment and reduces neurodegeneration in 5xFAD mice

(2022) Liuji Chen et al.   FREE RADICAL BIOLOGY AND MEDICINE

Microglia in Alzheimer’s Disease: An Unprecedented Opportunity as Prospective Drug Target

(2022) Bhargavi Kulkarni et al.   MOLECULAR NEUROBIOLOGY

PKCβII phosphorylates ACSL4 to amplify lipid peroxidation to induce ferroptosis

(2022) Hai-Liang Zhang et al.   NATURE CELL BIOLOGY

The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics

(2022) Eric Karran et al.   NATURE REVIEWS DRUG DISCOVERY

CD8+ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4

(2022) Peng Liao et al.   CANCER CELL

Selective ferroptosis vulnerability due to familial Alzheimer’s disease presenilin mutations

(2022) Mark A. Greenough et al.   CELL DEATH AND DIFFERENTIATION

Tau biomarkers in Alzheimer's disease: towards implementation in clinical practice and trials

(2022) Rik Ossenkoppele et al.   LANCET NEUROLOGY

Role of JAK-STAT and PPAR-Gamma Signalling Modulators in the Prevention of Autism and Neurological Dysfunctions

(2022) Rishabh Khera et al.   MOLECULAR NEUROBIOLOGY

Iron Dyshomeostasis and Ferroptosis: A New Alzheimer’s Disease Hypothesis?

(2022) Feixue Wang et al.   Frontiers in Aging Neuroscience

ACSL4 contributes to ferroptosis‐mediated rhabdomyolysis in exertional heat stroke

(2022) Sixiao He et al.   Journal of Cachexia Sarcopenia and Muscle

Microglia in the Neuroinflammatory Pathogenesis of Alzheimer’s Disease and Related Therapeutic Targets

(2022) Yongle Cai et al.   Frontiers in Immunology

ACSL4 deficiency confers protection against ferroptosis-mediated acute kidney injury

(2022) Yue Wang et al.   Redox Biology

Pioglitazone, Bladder Cancer, and the Presumption of Innocence

(2022) Georgios S. Papaetis   Current Drug Safety

ACSL4 exacerbates ischemic stroke by promoting ferroptosis-induced brain injury and neuroinflammation

(2021) Yu Cui et al.   BRAIN BEHAVIOR AND IMMUNITY

Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer’s disease

(2021) Wen-Dai Bao et al.   CELL DEATH AND DIFFERENTIATION

Ferroptosis: mechanisms, biology and role in disease

(2021) Xuejun Jiang et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Alzheimer's disease

(2021) Philip Scheltens et al.   LANCET

Mitochondrial aldehyde dehydrogenase (ALDH2) rescues cardiac contractile dysfunction in an APP/PS1 murine model of Alzheimer’s disease via inhibition of ACSL4-dependent ferroptosis

(2021) Zhi-yun Zhu et al.   ACTA PHARMACOLOGICA SINICA

Baicalin Prevents Myocardial Ischemia/Reperfusion Injury Through Inhibiting ACSL4 Mediated Ferroptosis

(2021) Zhenyu Fan et al.   Frontiers in Pharmacology

Neuroinflammation in Alzheimer’s Disease

(2021) Isaac G. Onyango et al.   Biomedicines

Pioglitazone use associated with reduced risk of the first attack of ischemic stroke in patients with newly onset type 2 diabetes: a nationwide nested case–control study

(2021) Junghee Ha et al.   Cardiovascular Diabetology

The protective effects of pioglitazone against cognitive impairment caused by L-Methionine administration in a rat model

(2021) Karem. Alzoubi et al.   CNS & Neurological Disorders-Drug Targets

Safety and efficacy of pioglitazone for the delay of cognitive impairment in people at risk of Alzheimer's disease (TOMMORROW): a prognostic biomarker study and a phase 3, randomised, double-blind, placebo-controlled trial

(2021) Daniel K Burns et al.   LANCET NEUROLOGY

Microglial activation and tau propagate jointly across Braak stages

(2021) Tharick A. Pascoal et al.   NATURE MEDICINE

The brain penetrant PPARγ agonist leriglitazone restores multiple altered pathways in models of X-linked adrenoleukodystrophy

(2021) Laura Rodríguez-Pascau et al.   Science Translational Medicine

Reassessment of Pioglitazone for Alzheimer’s Disease

(2021) Ann M. Saunders et al.   Frontiers in Neuroscience

Tetrahydroxy stilbene glycoside ameliorates Alzheimer’s disease in APP/PS1 mice via glutathione peroxidase related ferroptosis

(2021) Yan Gao et al.   INTERNATIONAL IMMUNOPHARMACOLOGY

Pioglitazone alleviates maternal sleep deprivation-induced cognitive deficits in male rat offspring by enhancing microglia-mediated neurogenesis

(2020) Yue Han et al.   BRAIN BEHAVIOR AND IMMUNITY

Iron dyshomeostasis, lipid peroxidation and perturbed expression of cystine/glutamate antiporter in Alzheimer’s disease: Evidence of ferroptosis

(2020) Azhaar Ashraf et al.   Redox Biology

Preventive and Therapeutic Strategies in Alzheimer's Disease: Focus on Oxidative Stress, Redox Metals, and Ferroptosis

(2020) Germán Plascencia-Villa et al.   ANTIOXIDANTS & REDOX SIGNALING

Pioglitazone for primary stroke prevention in Asian patients with type 2 diabetes and cardiovascular risk factors: a retrospective study

(2020) Yi-Chih Hung et al.   Cardiovascular Diabetology

Adipose depot-specific effects of 16 weeks of pioglitazone on in vivo adipogenesis in women with obesity: a randomised controlled trial

(2020) Ursula White et al.   DIABETOLOGIA

Inhibition of ACSL4 attenuates ferroptotic damage after pulmonary ischemia‐reperfusion

(2020) Yixin Xu et al.   FASEB JOURNAL

The Role of Microglia and the Nlrp3 Inflammasome in Alzheimer's Disease

(2020) Kendra L. Hanslik et al.   Frontiers in Neurology

CMS121, a fatty acid synthase inhibitor, protects against excess lipid peroxidation and inflammation and alleviates cognitive loss in a transgenic mouse model of Alzheimer's disease

(2020) Gamze Ates et al.   Redox Biology

Ferroptosis: molecular mechanisms and health implications

(2020) Daolin Tang et al.   CELL RESEARCH

Modulation of β-Amyloid Fibril Formation in Alzheimer’s Disease by Microglia and Infection

(2020) Madeleine R. Brown et al.   Frontiers in Molecular Neuroscience

Pioglitazone Therapy in Patients With Stroke and Prediabetes

(2019) J. David Spence et al.   JAMA Neurology

Brain iron is associated with accelerated cognitive decline in people with Alzheimer pathology

(2019) Scott Ayton et al.   MOLECULAR PSYCHIATRY

Scope of new formulation approaches in the repurposing of pioglitazone for the management of Alzheimer’s disease

(2019) Gifty M. Jojo et al.   JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS

Ischemia-induced ACSL4 activation contributes to ferroptosis-mediated tissue injury in intestinal ischemia/reperfusion

(2019) Yang Li et al.   CELL DEATH AND DIFFERENTIATION

CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy

(2019) Weimin Wang et al.   NATURE

Impact of TREM2 risk variants on brain region-specific immune activation and plaque microenvironment in Alzheimer’s disease patient brain samples

(2019) Stefan Prokop et al.   ACTA NEUROPATHOLOGICA

Effect of pioglitazone in acute ischemic stroke patients with diabetes mellitus: a nested case–control study

(2019) Min-Hee Woo et al.   Cardiovascular Diabetology

Activated PPARγ Abrogates Misprocessing of Amyloid Precursor Protein, Tau Missorting and Synaptotoxicity

(2019) Susanne Moosecker et al.   Frontiers in Cellular Neuroscience

Pioglitazone Reduces β Amyloid Levels via Inhibition of PPARγ Phosphorylation in a Neuronal Model of Alzheimer’s Disease

(2019) Qiankun Quan et al.   Frontiers in Aging Neuroscience

Alzheimer Disease: An Update on Pathobiology and Treatment Strategies

(2019) Justin M. Long et al.   CELL

The role of NLRP3 in traumatic brain injury and its regulation by pioglitazone

(2019) Ho Jun Yi et al.   JOURNAL OF NEUROSURGERY

FSP1 is a glutathione-independent ferroptosis suppressor

(2019) Sebastian Doll et al.   NATURE

The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis

(2019) Kirill Bersuker et al.   NATURE

NLRP3 inflammasome activation drives tau pathology

(2019) Christina Ising et al.   NATURE

Role of acyl-CoA synthetase ACSL4 in arachidonic acid metabolism

(2019) Hiroshi Kuwata et al.   PROSTAGLANDINS & OTHER LIPID MEDIATORS

Selenium Utilization by GPX4 Is Required to Prevent Hydroperoxide-Induced Ferroptosis

(2018) Irina Ingold et al.   CELL

Impact of treatment with pioglitazone on stroke outcomes: A real-world database analysis

(2018) Christopher Ll Morgan et al.   DIABETES OBESITY & METABOLISM

Comparative efficacy and acceptability of antidiabetic agents for Alzheimer's disease and mild cognitive impairment: A systematic review and network meta-analysis

(2018) Bing Cao et al.   DIABETES OBESITY & METABOLISM

Rosiglitazone as a Modulator of TLR4 and TLR3 Signaling Pathways in Rat Primary Neurons and Astrocytes

(2018) Dmitry Chistyakov et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

APOE4 Causes Widespread Molecular and Cellular Alterations Associated with Alzheimer’s Disease Phenotypes in Human iPSC-Derived Brain Cell Types

(2018) Yuan-Ta Lin et al.   NEURON

Unsolved mysteries: How does lipid peroxidation cause ferroptosis?

(2018) Huizhong Feng et al.   PLOS BIOLOGY

Effect of Pioglitazone in Combination with Moderate Dose Statin on Atherosclerotic Inflammation: Randomized Controlled Clinical Trial Using Serial FDG-PET/CT

(2018) Eun Ho Choo et al.   Korean Circulation Journal

Pioglitazone Use After Stroke

(2018) Jesse Dawson   CIRCULATION

The role of microglia in processing and spreading of bioactive tau seeds in Alzheimer’s disease

(2018) Sarah C. Hopp et al.   Journal of Neuroinflammation

Characterization of ferroptosis in murine models of hemochromatosis

(2017) Hao Wang et al.   HEPATOLOGY

Reactive Astrocytes: Production, Function, and Therapeutic Potential

(2017) Shane A. Liddelow et al.   IMMUNITY

Cortical Iron Reflects Severity of Alzheimer’s Disease

(2017) Sara van Duijn et al.   JOURNAL OF ALZHEIMERS DISEASE

Glial contributions to neurodegeneration in tauopathies

(2017) Cheryl E. G. Leyns et al.   Molecular Neurodegeneration

Alliin, a garlic organosulfur compound, ameliorates gut inflammation through MAPK-NF-κB/AP-1/STAT-1 inactivation and PPAR-γ activation

(2017) Limin Shi et al.   MOLECULAR NUTRITION & FOOD RESEARCH

Neurotoxic reactive astrocytes are induced by activated microglia

(2017) Shane A. Liddelow et al.   NATURE

Targeting Pioglitazone Hydrochloride Therapy After Stroke or Transient Ischemic Attack According to Pretreatment Risk for Stroke or Myocardial Infarction

(2017) Walter N. Kernan et al.   JAMA Neurology

Rosiglitazone Exerts an Anti-depressive Effect in Unpredictable Chronic Mild-Stress-Induced Depressive Mice by Maintaining Essential Neuron Autophagy and Inhibiting Excessive Astrocytic Apoptosis

(2017) Zhan Zhao et al.   Frontiers in Molecular Neuroscience

Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial

(2017) Olga Vaccaro et al.   Lancet Diabetes & Endocrinology

Ablation of ferroptosis regulator glutathione peroxidase 4 in forebrain neurons promotes cognitive impairment and neurodegeneration

(2017) William Sealy Hambright et al.   Redox Biology

On the Mechanism of Cytoprotection by Ferrostatin-1 and Liproxstatin-1 and the Role of Lipid Peroxidation in Ferroptotic Cell Death

(2017) Omkar Zilka et al.   ACS Central Science

Pioglitazone Prevents Stroke in Patients With a Recent Transient Ischemic Attack or Ischemic Stroke

(2017) Shadi Yaghi et al.   CIRCULATION

The antidepressant-like effects of pioglitazone in a chronic mild stress mouse model are associated with PPARγ-mediated alteration of microglial activation phenotypes

(2016) Qiuying Zhao et al.   Journal of Neuroinflammation

Astrocyte-Microglia Cross Talk through Complement Activation Modulates Amyloid Pathology in Mouse Models of Alzheimer's Disease

(2016) H. Lian et al.   JOURNAL OF NEUROSCIENCE

Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis

(2016) Valerian E Kagan et al.   Nature Chemical Biology

ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition

(2016) Sebastian Doll et al.   Nature Chemical Biology

Pioglitazone after Ischemic Stroke or Transient Ischemic Attack

(2016) Walter N. Kernan et al.   NEW ENGLAND JOURNAL OF MEDICINE

Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis

(2016) Wan Seok Yang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Pioglitazone for Secondary Stroke Prevention

(2016) Meng Lee et al.   STROKE

Editorial: Impact of Lipid Peroxidation on the Physiology and Pathophysiology of Cell Membranes

(2016) Angel Catalá et al.   Frontiers in Physiology

Human Haploid Cell Genetics Reveals Roles for Lipid Metabolism Genes in Nonapoptotic Cell Death

(2015) Scott J. Dixon et al.   ACS Chemical Biology

Effect of pioglitazone medication on the incidence of dementia

(2015) Michael T. Heneka et al.   ANNALS OF NEUROLOGY

Brain Glutathione Levels – A Novel Biomarker for Mild Cognitive Impairment and Alzheimer’s Disease

(2015) Pravat K. Mandal et al.   BIOLOGICAL PSYCHIATRY

Favorable Impact on LDL Particle Size in Response to Treatment With Pioglitazone is Associated With Less Progression of Coronary Atherosclerosis in Patients With Type 2 Diabetes

(2015) Preethi Mani et al.   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

Neuroinflammation in Alzheimer's disease

(2015) Michael T Heneka et al.   LANCET NEUROLOGY

Depletion of microglia and inhibition of exosome synthesis halt tau propagation

(2015) Hirohide Asai et al.   NATURE NEUROSCIENCE

NFκB-Activated Astroglial Release of Complement C3 Compromises Neuronal Morphology and Function Associated with Alzheimer’s Disease

(2015) Hong Lian et al.   NEURON

Anti-Diabetes Drug Pioglitazone Ameliorates Synaptic Defects in AD Transgenic Mice by Inhibiting Cyclin-Dependent Kinase5 Activity

(2015) Jinan Chen et al.   PLoS One

Regulation of Ferroptotic Cancer Cell Death by GPX4

(2014) Wan Seok Yang et al.   CELL

Pioglitazone Prevents the Endothelial Dysfunction Induced by Ischemia and Reperfusion in Healthy Subjects

(2014) Yuka Sakatani et al.   JOURNAL OF CARDIOVASCULAR PHARMACOLOGY

Ferrostatins Inhibit Oxidative Lipid Damage and Cell Death in Diverse Disease Models

(2014) Rachid Skouta et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Sustained 4-year Cognitive and Functional Response in Early Alzheimer's Disease with Pioglitazone

(2014) Stephen Read et al.   JOURNAL OF THE AMERICAN GERIATRICS SOCIETY

Pharmacological inhibition of cystine–glutamate exchange induces endoplasmic reticulum stress and ferroptosis

(2014) Scott J Dixon et al.   eLife

The physiological functions of iron regulatory proteins in iron homeostasis - an update

(2014) De-Liang Zhang et al.   Frontiers in Pharmacology

Microglia convert aggregated amyloid-β into neurotoxic forms through the shedding of microvesicles

(2013) P Joshi et al.   CELL DEATH AND DIFFERENTIATION

Sustained Interleukin-1  Overexpression Exacerbates Tau Pathology Despite Reduced Amyloid Burden in an Alzheimer's Mouse Model

(2013) S. Ghosh et al.   JOURNAL OF NEUROSCIENCE

Pioglitazone Decreases Coronary Artery Inflammation in Impaired Glucose Tolerance and Diabetes Mellitus

(2013) Yoshikazu Nitta et al.   JACC-Cardiovascular Imaging

The systemic iron-regulatory proteins hepcidin and ferroportin are reduced in the brain in Alzheimer’s disease

(2013) Animesh Raha et al.   Acta Neuropathologica Communications

The Classification of Microglial Activation Phenotypes on Neurodegeneration and Regeneration in Alzheimer’s Disease Brain

(2012) Megan M. Varnum et al.   ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS

Pioglitazone Slows Progression of Atherosclerosis in Prediabetes Independent of Changes in Cardiovascular Risk Factors

(2012) Aramesh Saremi et al.   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

Long-chain acyl-CoA synthetase 4 is regulated by phosphorylation

(2012) María Emilia Smith et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death

(2012) Scott J. Dixon et al.   CELL

The PPAR-gamma agonist pioglitazone protects cortical neurons from inflammatory mediators via improvement in peroxisomal function

(2012) Elizabeth Gray et al.   Journal of Neuroinflammation

Pro-inflammatory interleukin-18 increases Alzheimer’s disease-associated amyloid-β production in human neuron-like cells

(2012) Elina M Sutinen et al.   Journal of Neuroinflammation

PPAR /RXR -Induced and CD36-Mediated Microglial Amyloid-  Phagocytosis Results in Cognitive Improvement in Amyloid Precursor Protein/Presenilin 1 Mice

(2012) M. Yamanaka et al.   JOURNAL OF NEUROSCIENCE

Genomic Analysis of Reactive Astrogliosis

(2012) J. L. Zamanian et al.   JOURNAL OF NEUROSCIENCE

Mechanisms Underlying the Rapid Peroxisome Proliferator-Activated Receptor- -Mediated Amyloid Clearance and Reversal of Cognitive Deficits in a Murine Model of Alzheimer's Disease

(2012) S. Mandrekar-Colucci et al.   JOURNAL OF NEUROSCIENCE

NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice

(2012) Michael T. Heneka et al.   NATURE

Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export

(2012) Peng Lei et al.   NATURE MEDICINE

The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: nested case-control study

(2012) L. Azoulay et al.   BMJ-British Medical Journal

Multiple cellular and molecular mechanisms Are involved in human Aβ clearance by transplanted adult astrocytes

(2011) Rea Pihlaja et al.   GLIA

Seeding of Normal Tau by Pathological Tau Conformers Drives Pathogenesis of Alzheimer-like Tangles

(2011) Jing L. Guo et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Stages of the Pathologic Process in Alzheimer Disease: Age Categories From 1 to 100 Years

(2011) Heiko Braak et al.   JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY

In Vivo Positron Emission Tomographic Imaging of Glial Responses to Amyloid-  and Tau Pathologies in Mouse Models of Alzheimer's Disease and Related Disorders

(2011) J. Maeda et al.   JOURNAL OF NEUROSCIENCE

Lowering the Triglyceride/High-Density Lipoprotein Cholesterol Ratio Is Associated With the Beneficial Impact of Pioglitazone on Progression of Coronary Atherosclerosis in Diabetic Patients

(2011) Stephen J. Nicholls et al.   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

Pioglitazone and bladder cancer

(2011) Dominique Hillaire-Buys et al.   LANCET

Pioglitazone Attenuates Atherosclerotic Plaque Inflammation in Patients With Impaired Glucose Tolerance or Diabetes

(2011) Minori Mizoguchi et al.   JACC-Cardiovascular Imaging

A Randomized Pilot Clinical Trial of the Safety of Pioglitazone in Treatment of Patients With Alzheimer Disease

(2010) David S. Geldmacher et al.   ARCHIVES OF NEUROLOGY

Iron-Export Ferroxidase Activity of β-Amyloid Precursor Protein Is Inhibited by Zinc in Alzheimer's Disease

(2010) James A. Duce et al.   CELL

Rosiglitazone Rescues Memory Impairment in Alzheimer's Transgenic Mice: Mechanisms Involving a Reduced Amyloid and Tau Pathology

(2010) Luis Escribano et al.   NEUROPSYCHOPHARMACOLOGY

Accumulation of tau induced in neurites by microglial proinflammatory mediators

(2009) Philipp Gorlovoy et al.   FASEB JOURNAL

Activation of Wnt signaling by lithium and rosiglitazone reduced spatial memory impairment and neurodegeneration in brains of an APPswe/PSEN1ΔE9 mouse model of Alzheimer's disease

(2009) E M Toledo et al.   MOLECULAR PSYCHIATRY

Efficacy of PPAR-γ agonist pioglitazone in mild Alzheimer disease

(2009) Tomohiko Sato et al.   NEUROBIOLOGY OF AGING

Glutathione Peroxidase 4 Senses and Translates Oxidative Stress into 12/15-Lipoxygenase Dependent- and AIF-Mediated Cell Death

(2008) Alexander Seiler et al.   Cell Metabolism

Synthetic Lethal Screening Identifies Compounds Activating Iron-Dependent, Nonapoptotic Cell Death in Oncogenic-RAS-Harboring Cancer Cells

(2008) Wan Seok Yang et al.   CHEMISTRY & BIOLOGY

Comparison of Pioglitazone vs Glimepiride on Progression of Coronary Atherosclerosis in Patients With Type 2 Diabetes

(2008) Steven E. Nissen et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

The role of interleukin-1 in neuroinflammation and Alzheimer disease: an evolving perspective

(2008) Solomon S Shaftel et al.   Journal of Neuroinflammation

Complete Rescue of Cerebrovascular Function in Aged Alzheimer's Disease Transgenic Mice by Antioxidants and Pioglitazone, a Peroxisome Proliferator-Activated Receptor   Agonist

(2008) N. Nicolakakis et al.   JOURNAL OF NEUROSCIENCE