Repurposing metformin to treat age-related neurodegenerative disorders and ischemic stroke

Novel approaches for the delivery of therapeutics in ischemic stroke

(2020) Saeideh Nozohouri et al.   DRUG DISCOVERY TODAY

Implicating endothelial cell senescence to dysfunction in the ageing and diseased brain

(2020) Sara I. Graves et al.   BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY

Smoking Cessation—Progress, Barriers, and New Opportunities

(2020) Jerome M. Adams   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Metformin Ameliorates Aβ Pathology by Insulin-Degrading Enzyme in a Transgenic Mouse Model of Alzheimer’s Disease

(2020) Xin-Yi Lu et al.   Oxidative Medicine and Cellular Longevity

Exosomes in Ischemic Stroke

(2020) Saeideh Nozohouri et al.   CURRENT PHARMACEUTICAL DESIGN

Metformin reduces neuronal damage and promotes neuroblast proliferation and differentiation in a cerebral ischemia/reperfusion rat model

(2019) Rui Yuan et al.   NEUROREPORT

Neuro-Protective Role of Metformin in Patients with Acute Stroke and Type 2 Diabetes Mellitus via AMPK/Mammalian Target of Rapamycin (mTOR) Signaling Pathway and Oxidative Stress

(2019) Min Zhao et al.   MEDICAL SCIENCE MONITOR

NF-κB as the mediator of metformin's effect on ageing and ageing-related diseases

(2019) Gönül Kanigur Sultuybek et al.   CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY

Age-Associated Changes in the Immune System and Blood–Brain Barrier Functions

(2019) Michelle Erickson et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Metformin in 2019

(2019) James Flory et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Oligoprotective effect of metformin through the AMPK-dependent on restoration of mitochondrial hemostasis in the cuprizone-induced multiple sclerosis model

(2019) Seyed Hossein Hosseini Largani et al.   JOURNAL OF MOLECULAR HISTOLOGY

Trends in clinical success rates and therapeutic focus

(2019) Helen Dowden et al.   NATURE REVIEWS DRUG DISCOVERY

The Potential of Flavonoids for the Treatment of Neurodegenerative Diseases

(2019) Pamela Maher   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

FO081METFORMIN ALLEVIATES STROKE SEVERITY IN FEMALE MICE WITH CHRONIC KIDNEY DISEASE THROUGH AMPK ACTIVATION AND SUBSEQUENT DECREASE OF MICROGLIA/MACROPHAGES M1 POLARIZATION

(2019) Maria Grissi et al.   NEPHROLOGY DIALYSIS TRANSPLANTATION

The beneficial roles of metformin on the brain with cerebral ischaemia/reperfusion injury

(2019) Tom Leech et al.   PHARMACOLOGICAL RESEARCH

Metformin Restores CNS Remyelination Capacity by Rejuvenating Aged Stem Cells

(2019) Björn Neumann et al.   Cell Stem Cell

Expanding therapeutic opportunities for neurodegenerative diseases: A perspective on the important role of phenotypic screening

(2019) Susanne E. Swalley   BIOORGANIC & MEDICINAL CHEMISTRY

Prenatal electronic cigarette exposure decreases brain glucose utilization and worsens outcome in offspring hypoxic–ischemic brain injury

(2019) Ali E. Sifat et al.   JOURNAL OF NEUROCHEMISTRY

Metformin Protects against Oxidative Stress Injury Induced by Ischemia/Reperfusion via Regulation of the lncRNA-H19/miR-148a-3p/Rock2 Axis

(2019) Jing Zeng et al.   Oxidative Medicine and Cellular Longevity

Intestinal macrophages and their interaction with the enteric nervous system in health and Inflammatory Bowel Disease

(2018) Elisa Meroni et al.   Acta Physiologica

Metformin treatment prevents amyloid plaque deposition and memory impairment in APP/PS1 mice

(2018) Zhenri Ou et al.   BRAIN BEHAVIOR AND IMMUNITY

Role of microglia under cardiac and cerebral ischemia/reperfusion (I/R) injury

(2018) Poomarin Surinkaew et al.   METABOLIC BRAIN DISEASE

RIP1K Contributes to Neuronal and Astrocytic Cell Death in Ischemic Stroke via Activating Autophagic-lysosomal Pathway

(2018) Yong Ni et al.   NEUROSCIENCE

Defective cholesterol clearance limits remyelination in the aged central nervous system

(2018) Ludovico Cantuti-Castelvetri et al.   SCIENCE

Mechanisms of metformin action: In and out of the gut

(2018) Takahiro Minamii et al.   Journal of Diabetes Investigation

Neurovascular unit transport responses to ischemia and common coexisting conditions: smoking and diabetes

(2018) Ali E Sifat et al.   AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY

Endothelial cell senescence in aging-related vascular dysfunction

(2018) Guanghong Jia et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

Metformin as geroprotector: experimental and clinical evidence

(2018) Veronika Piskovatska et al.   BIOGERONTOLOGY

Incidence of Dementia is Increased in Type 2 Diabetes and Reduced by the Use of Sulfonylureas and Metformin

(2018) Chih-Cheng Hsu et al.   JOURNAL OF ALZHEIMERS DISEASE

Nicotine & electronic cigarette (E-Cig) exposure decreases brain glucose utilization in ischemic stroke

(2018) Ali E. Sifat et al.   JOURNAL OF NEUROCHEMISTRY

Divergent Effects of Metformin on an Inflammatory Model of Parkinson’s Disease

(2018) Khadija Tayara et al.   Frontiers in Cellular Neuroscience

Metformin — a new old drug

(2017) Marta Patrycja Wróbel et al.   Endokrynologia Polska

Involvement of arterial baroreflex and nicotinic acetylcholine receptor α7 subunit pathway in the protection of metformin against stroke in stroke-prone spontaneously hypertensive rats

(2017) Jin-Min Guo et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

Effect of Metformin on Adult Hippocampal Neurogenesis: Comparison with Donepezil and Links to Cognition

(2017) Sara Ahmed et al.   JOURNAL OF MOLECULAR NEUROSCIENCE

Epidemiologie und Ursachen der Parkinson-Erkrankung

(2017) C. M. Lill et al.   NERVENARZT

Metformin lowers α-synuclein phosphorylation and upregulates neurotrophic factor in the MPTP mouse model of Parkinson's disease

(2017) Nikita Katila et al.   NEUROPHARMACOLOGY

Metformin protects the brain against ischemia/reperfusion injury through PI3K/Akt1/JNK3 signaling pathways in rats

(2017) Xu-Hua Ge et al.   PHYSIOLOGY & BEHAVIOR

Metformin treatment after the hypoxia-ischemia attenuates brain injury in newborn rats

(2017) Mingchu Fang et al.   Oncotarget

Activation of the ATF2/CREB-PGC-1α pathway by metformin leads to dopaminergic neuroprotection

(2017) Hojin Kang et al.   Oncotarget

Role of Nrf2 and protective effects of Metformin against tobacco smoke-induced cerebrovascular toxicity

(2017) Shikha Prasad et al.   Redox Biology

Offsetting the impact of smoking and e-cigarette vaping on the cerebrovascular system and stroke injury: Is Metformin a viable countermeasure?

(2017) Mohammad A. Kaisar et al.   Redox Biology

The Cellular Phase of Alzheimer’s Disease

(2016) Bart De Strooper et al.   CELL

Metformin activation of AMPK-dependent pathways is neuroprotective in human neural stem cells against Amyloid-beta-induced mitochondrial dysfunction

(2016) Ming-Chang Chiang et al.   EXPERIMENTAL CELL RESEARCH

Metformin Prevents Dopaminergic Neuron Death in MPTP/P-Induced Mouse Model of Parkinson’s Disease via Autophagy and Mitochondrial ROS Clearance

(2016) Ming Lu et al.   INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY

Metformin ameliorates the development of experimental autoimmune encephalomyelitis by regulating T helper 17 and regulatory T cells in mice

(2016) Yafei Sun et al.   JOURNAL OF NEUROIMMUNOLOGY

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

Ageing, neurodegeneration and brain rejuvenation

(2016) Tony Wyss-Coray   NATURE

Pre-stroke Metformin Treatment is Neuroprotective Involving AMPK Reduction

(2016) Tian Deng et al.   NEUROCHEMICAL RESEARCH

Antidiabetic drugs restore abnormal transport of amyloid-β across the blood–brain barrier and memory impairment in db / db mice

(2016) Fang Chen et al.   NEUROPHARMACOLOGY

Reasons for Trying E-cigarettes and Risk of Continued Use

(2016) K. W. Bold et al.   PEDIATRICS

Metformin pretreatment enhanced learning and memory in cerebral forebrain ischaemia: the role of the AMPK/BDNF/P70SK signalling pathway

(2016) Negar Ghadernezhad et al.   PHARMACEUTICAL BIOLOGY

White matter injury in ischemic stroke

(2016) Yuan Wang et al.   PROGRESS IN NEUROBIOLOGY

Epidemiology of multiple sclerosis

(2016) E. Leray et al.   REVUE NEUROLOGIQUE

Vascular Cell Senescence Contributes to Blood–Brain Barrier Breakdown

(2016) Yu Yamazaki et al.   STROKE

AMPK antagonizes hepatic glucagon-stimulated cyclic AMP signalling via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B

(2016) M. Johanns et al.   Nature Communications

Mechanisms of Aβ Clearance and Degradation by Glial Cells

(2016) Miriam Ries et al.   Frontiers in Aging Neuroscience

Therapeutic Manipulation of Ageing: Repurposing Old Dogs and Discovering New Tricks

(2016) Venkatesh Mallikarjun et al.   EBioMedicine

Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease

(2015) Alexey Moskalev et al.   Aging-US

Metformin increases APP expression and processing via oxidative stress, mitochondrial dysfunction and NF-κB activation: Use of insulin to attenuate metformin's effect

(2015) Pasquale Picone et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

Antidiabetic agents: Potential anti-inflammatory activity beyond glucose control

(2015) A.J. Scheen et al.   DIABETES & METABOLISM

Metformin improves anxiety-like behaviors through AMPK-dependent regulation of autophagy following transient forebrain ischemia

(2015) Alireza Sarkaki et al.   METABOLIC BRAIN DISEASE

Targeting Adenosine Monophosphate-Activated Protein Kinase by Metformin Adjusts Post-Ischemic Hyperemia and Extracellular Neuronal Discharge in Transient Global Cerebral Ischemia

(2015) Yaghoob Farbood et al.   MICROCIRCULATION

Novel Stroke Therapeutics: Unraveling Stroke Pathophysiology and Its Impact on Clinical Treatments

(2015) Paul M. George et al.   NEURON

Blood–brain barrier dysfunction developed during normal aging is associated with inflammation and loss of tight junctions but not with leukocyte recruitment

(2015) Mina Elahy et al.   Immunity & Ageing

Decrease in Plasma Levels of α-Synuclein Is Evident in Patients with Parkinson’s Disease after Elimination of Heterophilic Antibody Interference

(2015) Ryotaro Ishii et al.   PLoS One

The neurovascular unit - concept review

(2014) V. Muoio et al.   Acta Physiologica

Oxidative and pro-inflammatory impact of regular and denicotinized cigarettes on blood brain barrier endothelial cells: is smoking reduced or nicotine-free products really safe?

(2014) Pooja Naik et al.   BMC NEUROSCIENCE

Improvement of functional recovery by chronic metformin treatment is associated with enhanced alternative activation of microglia/macrophages and increased angiogenesis and neurogenesis following experimental stroke

(2014) Qin Jin et al.   BRAIN BEHAVIOR AND IMMUNITY

Acute metformin preconditioning confers neuroprotection against focal cerebral ischaemia by pre-activation of AMPK-dependent autophagy

(2014) Teng Jiang et al.   BRITISH JOURNAL OF PHARMACOLOGY

Metformin: From Mechanisms of Action to Therapies

(2014) Marc Foretz et al.   Cell Metabolism

Metformin Treatment in the Period After Stroke Prevents Nitrative Stress and Restores Angiogenic Signaling in the Brain in Diabetes

(2014) Mohammed Abdelsaid et al.   DIABETES

Chronic metformin treatment improves post-stroke angiogenesis and recovery after experimental stroke

(2014) Venugopal R. Venna et al.   EUROPEAN JOURNAL OF NEUROSCIENCE

Glial Scar Formation Occurs in the Human Brain after Ischemic Stroke

(2014) Lijie Huang et al.   International Journal of Medical Sciences

Metformin attenuates blood-brain barrier disruption in mice following middle cerebral artery occlusion

(2014) Yanqun Liu et al.   Journal of Neuroinflammation

Pre-treatment with metformin activates Nrf2 antioxidant pathways and inhibits inflammatory responses through induction of AMPK after transient global cerebral ischemia

(2014) Ghorbangol Ashabi et al.   METABOLIC BRAIN DISEASE

Activation of AMP-activated protein kinase by metformin protects against global cerebral ischemia in male rats: Interference of AMPK/PGC-1α pathway

(2014) Ghorbangol Ashabi et al.   METABOLIC BRAIN DISEASE

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(2014) Ben Lu et al.   MOLECULAR MEDICINE

Chronic Metformin Preconditioning Provides Neuroprotection via Suppression of NF-κB-Mediated Inflammatory Pathway in Rats with Permanent Cerebral Ischemia

(2014) Xi-Chen Zhu et al.   MOLECULAR NEUROBIOLOGY

Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase

(2014) Anila K. Madiraju et al.   NATURE

Stem cell aging: mechanisms, regulators and therapeutic opportunities

(2014) Juhyun Oh et al.   NATURE MEDICINE

Microglial and macrophage polarization—new prospects for brain repair

(2014) Xiaoming Hu et al.   Nature Reviews Neurology

Neuroprotective effect of metformin in MPTP-induced Parkinson’s disease in mice

(2014) S.P. Patil et al.   NEUROSCIENCE

Metformin promotes focal angiogenesis and neurogenesis in mice following middle cerebral artery occlusion

(2014) Yanqun Liu et al.   NEUROSCIENCE LETTERS

The dual role of astrocyte activation and reactive gliosis

(2014) Milos Pekny et al.   NEUROSCIENCE LETTERS

Quantification of metformin by the HPLC method in brain regions, cerebrospinal fluid and plasma of rats treated with lipopolysaccharide

(2014) Krzysztof Łabuzek et al.   Pharmacological Reports

Insufficient OPC migration into demyelinated lesions is a cause of poor remyelination in MS and mouse models

(2013) Amanda Boyd et al.   ACTA NEUROPATHOLOGICA

Metformin inhibits the senescence-associated secretory phenotype by interfering with IKK/NF-κB activation

(2013) Olga Moiseeva et al.   AGING CELL

AMP-Activated Protein Kinase Signaling Protects Oligodendrocytes that Restore Central Nervous System Functions in an Experimental Autoimmune Encephalomyelitis Model

(2013) Ajaib S. Paintlia et al.   AMERICAN JOURNAL OF PATHOLOGY

Defective quality control mechanisms and accumulation of damaged mitochondria link Gaucher and Parkinson diseases

(2013) Laura D Osellame et al.   Autophagy

Interaction between pericytes and endothelial cells leads to formation of tight junction in hyaloid vessels

(2013) Dong Hyun Jo et al.   MOLECULES AND CELLS

mTOR is a key modulator of ageing and age-related disease

(2013) Simon C. Johnson et al.   NATURE

Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin

(2013) Morgan D Fullerton et al.   NATURE MEDICINE

Autophagy and apoptosis dysfunction in neurodegenerative disorders

(2013) Saeid Ghavami et al.   PROGRESS IN NEUROBIOLOGY

Vascularization Pattern After Ischemic Stroke is Different in Control Versus Diabetic Rats

(2013) Roshini Prakash et al.   STROKE

Metformin improves healthspan and lifespan in mice

(2013) Alejandro Martin-Montalvo et al.   Nature Communications

Montreal Cognitive Assessment Is Superior to Standardized Mini-Mental Status Exam in Detecting Mild Cognitive Impairment in the Middle-Aged and Elderly Patients with Type 2 Diabetes Mellitus

(2013) Kannayiram Alagiakrishnan et al.   Biomed Research International

Brain Insulin Resistance and Deficiency as Therapeutic Targets in Alzheimers Disease

(2012) Suzanne M. de la Monte   Current Alzheimer Research

NF-κB inhibition delays DNA damage–induced senescence and aging in mice

(2012) Jeremy S. Tilstra et al.   JOURNAL OF CLINICAL INVESTIGATION

AMPK: a nutrient and energy sensor that maintains energy homeostasis

(2012) D. Grahame Hardie et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Neuroprotection and repair in multiple sclerosis

(2012) Robin J. M. Franklin et al.   Nature Reviews Neurology

Metformin attenuates Alzheimer's disease-like neuropathology in obese, leptin-resistant mice

(2012) Jiejie Li et al.   PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR

Exploiting drug-disease relationships for computational drug repositioning

(2011) J. T. Dudley et al.   BRIEFINGS IN BIOINFORMATICS

Clinical Pharmacokinetics of Metformin

(2011) Garry G. Graham et al.   CLINICAL PHARMACOKINETICS

Oxidative Stress Increases Blood—Brain Barrier Permeability and Induces Alterations in Occludin during Hypoxia—Reoxygenation

(2011) Jeffrey J Lochhead et al.   JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders

(2011) Berislav V. Zlokovic   NATURE REVIEWS NEUROSCIENCE

Peripheral insulin-sensitizer drug metformin ameliorates neuronal insulin resistance and Alzheimer’s-like changes

(2011) Amit Gupta et al.   NEUROPHARMACOLOGY

Ageing and neurodegenerative diseases

(2010) Chia-Wei Hung et al.   AGEING RESEARCH REVIEWS

The importance of regulation of blood glucose levels through activation of peripheral 5′-AMP-activated protein kinase on ischemic neuronal damage

(2010) Shinichi Harada et al.   BRAIN RESEARCH

Oxidative Stress and Diabetic Complications

(2010) Ferdinando Giacco et al.   CIRCULATION RESEARCH

Dysfunction of the Cholinergic Anti-Inflammatory Pathway Mediates Organ Damage in Hypertension

(2010) Dong-Jie Li et al.   HYPERTENSION

Vascular Protection in Diabetic Stroke: Role of Matrix Metalloprotease-Dependent Vascular Remodeling

(2010) Mostafa M Elgebaly et al.   JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

Pericytes regulate the blood–brain barrier

(2010) Annika Armulik et al.   NATURE

The Science of Stroke: Mechanisms in Search of Treatments

(2010) Michael A. Moskowitz et al.   NEURON

Review: Cerebral microvascular pathology in ageing and neurodegeneration

(2010) W. R. Brown et al.   NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY

Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling

(2010) E. Kickstein et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Effects of Metformin in Experimental Stroke

(2010) Jun Li et al.   STROKE

Oxidative stress in the brain of nicotine-induced toxicity: protective role of Andrographis paniculata Nees and vitamin E

(2009) Subhasis Das et al.   Applied Physiology Nutrition and Metabolism

Metformin Attenuated the Autoimmune Disease of the Central Nervous System in Animal Models of Multiple Sclerosis

(2009) N. Nath et al.   JOURNAL OF IMMUNOLOGY

Nicotine Exacerbates Brain Edema during In Vitro and In Vivo Focal Ischemic Conditions

(2009) J. R. Paulson et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Blood-brain barrier alterations in ageing and dementia

(2009) Bogdan O. Popescu et al.   JOURNAL OF THE NEUROLOGICAL SCIENCES

Inflammatory mechanisms in ischemic stroke: therapeutic approaches

(2009) Shaheen E Lakhan et al.   Journal of Translational Medicine

Structure and function of the blood–brain barrier

(2009) N. Joan Abbott et al.   NEUROBIOLOGY OF DISEASE

Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription

(2009) Y. Chen et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Granulocyte Colony-Stimulating Factor (G-CSF) for Cardio- and Cerebrovascular Regenerative Applications

(2008) Rainer Klocke et al.   CURRENT MEDICINAL CHEMISTRY

Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes

(2008) D. M. Nathan et al.   DIABETES CARE

Parkinson's disease: clinical features and diagnosis

(2008) J Jankovic   JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY

Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency

(2008) Siming Shen et al.   NATURE NEUROSCIENCE

ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration

(2008) Zhihui Zhong et al.   NATURE NEUROSCIENCE