Metformin in Alzheimer’s disease: An overview of potential mechanisms, preclinical and clinical findings

mTOR inhibition: a double-edged sword in patients with COVID-19?

(2021) Morteza Ghasemnejad-Berenji   Human Cell

Metformin attenuates plaque-associated tau pathology and reduces amyloid-β burden in APP/PS1 mice

(2021) Yanxing Chen et al.   Alzheimers Research & Therapy

Common Peripheral Immunity Mechanisms in Multiple Sclerosis and Alzheimer's Disease

(2021) Barbara Rossi et al.   Frontiers in Immunology

The effects of metformin on autophagy

(2021) Guangli Lu et al.   BIOMEDICINE & PHARMACOTHERAPY

Anticancer potential of metformin: focusing on gastrointestinal cancers

(2021) Mohammad rafi Khezri et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Pretreatment with metformin prevents microcystin‐LR ‐induced tau hyperphosphorylation via mTOR ‐dependent PP2A and GSK ‐3β activation

(2021) Yali Zhang et al.   ENVIRONMENTAL TOXICOLOGY

Metformin Attenuates High Glucose‐Induced Coronary Vascular Endothelial Hyper Permeability Via Inhibition of Orai‐1 Mediated Store‐Operated Calcium Entry

(2020) Shamsideen Ali et al.   FASEB JOURNAL

TREM2 activation attenuates neuroinflammation and neuronal apoptosis via PI3K/Akt pathway after intracerebral hemorrhage in mice

(2020) Shengpan Chen et al.   Journal of Neuroinflammation

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

Metformin Ameliorates Synaptic Defects in a Mouse Model of AD by Inhibiting Cdk5 Activity

(2020) YaLi Wang et al.   Frontiers in Cellular Neuroscience

Relationships between memory decline and the use of metformin or DPP4 inhibitors in people with type 2 diabetes with normal cognition or Alzheimer's disease, and the role APOE carrier status

(2020) Che‐Yuan Wu et al.   Alzheimers & Dementia

TREM2 overexpression rescues cognitive deficits in APP/PS1 transgenic mice by reducing neuroinflammation via the JAK/STAT/SOCS signaling pathway

(2020) John Bosco Ruganzu et al.   EXPERIMENTAL NEUROLOGY

Gene expression and functional deficits underlie TREM2-knockout microglia responses in human models of Alzheimer’s disease

(2020) Amanda McQuade et al.   Nature Communications

Metformin Promotes Neuronal Differentiation via Crosstalk between Cdk5 and Sox6 in Neuroblastoma Cells

(2019) Thunwa Binlateh et al.   Evidence-based Complementary and Alternative Medicine

Emerging pathways to neurodegeneration: Dissecting the critical molecular mechanisms in Alzheimer’s disease, Parkinson’s disease

(2019) Sean Hong Tan et al.   BIOMEDICINE & PHARMACOTHERAPY

Metformin Enhances Autophagy and Provides Cardioprotection in δ-Sarcoglycan Deficiency-Induced Dilated Cardiomyopathy

(2019) Hiromitsu Kanamori et al.   Circulation-Heart Failure

Metformin inhibits IL-6 signaling by decreasing IL-6R expression on multiple myeloma cells

(2019) Ameet K. Mishra et al.   LEUKEMIA

Metformin inhibits Aβ 25‐35 ‐induced apoptotic cell death in SH‐SY5Y cells

(2019) Li‐Xia Li et al.   BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY

Metformin Improves Learning and Memory in the SAMP8 Mouse Model of Alzheimer’s Disease

(2019) Susan A. Farr et al.   JOURNAL OF ALZHEIMERS DISEASE

ERβ promotes Aβ degradation via the modulation of autophagy

(2019) Yong Wei et al.   Cell Death & Disease

Altered Insulin Signaling in Alzheimer’s Disease Brain – Special Emphasis on PI3K-Akt Pathway

(2019) Sami Gabbouj et al.   Frontiers in Neuroscience

Metformin and risk of Alzheimer’s disease among community-dwelling people with diabetes: a national case-control study

(2019) Janet K Sluggett et al.   JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM

Potential microRNA-related targets in clearance pathways of amyloid-β: novel therapeutic approach for the treatment of Alzheimer’s disease

(2019) Soheil Madadi et al.   Cell and Bioscience

Synergistic effect of rapamycin and metformin against germ cell apoptosis and oxidative stress after testicular torsion/detorsion-induced ischemia/reperfusion in rats

(2018) Morteza Ghasemnejad-berenji et al.   BIOMEDICINE & PHARMACOTHERAPY

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

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

TREM2 inhibits inflammatory responses in mouse microglia by suppressing the PI3K/NF-κB signaling

(2018) Caixia Li et al.   CELL BIOLOGY INTERNATIONAL

ROS responsive resveratrol delivery from LDLR peptide conjugated PLA-coated mesoporous silica nanoparticles across the blood–brain barrier

(2018) Yang Shen et al.   JOURNAL OF NANOBIOTECHNOLOGY

Role of TNF–TNF Receptor 2 Signal in Regulatory T Cells and Its Therapeutic Implications

(2018) Sujuan Yang et al.   Frontiers in Immunology

Naringin Activates AMPK Resulting in Altered Expression of SREBPs, PCSK9, and LDLR To Reduce Body Weight in Obese C57BL/6J Mice

(2018) Guo-Guang Sui et al.   JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

Decreased Expression of Cathepsin D in Monocytes is Related to the Defective Degradation of Amyloid-β in Alzheimer's Disease

(2018) Li Tian et al.   JOURNAL OF ALZHEIMERS DISEASE

Metformin Use Associated with Reduced Risk of Dementia in Patients with Diabetes: A Systematic Review and Meta-Analysis

(2018) Jared M. Campbell et al.   JOURNAL OF ALZHEIMERS DISEASE

Metformin Inhibits Chemokine Expression Through the AMPK/NF-κB Signaling Pathway

(2018) Jinhui Ye et al.   JOURNAL OF INTERFERON AND CYTOKINE RESEARCH

Microglial TREM2/DAP12 Signaling: A Double-Edged Sword in Neural Diseases

(2018) Hiroyuki Konishi et al.   Frontiers in Cellular Neuroscience

High‐affinity interactions and signal transduction between Aβ oligomers and TREM2

(2018) Christian B Lessard et al.   EMBO Molecular Medicine

Metformin attenuates diabetes-induced tau hyperphosphorylation in vitro and in vivo by enhancing autophagic clearance

(2018) Jin-Liang Chen et al.   EXPERIMENTAL NEUROLOGY

New insights into the role of TREM2 in Alzheimer’s disease

(2018) Maud Gratuze et al.   Molecular Neurodegeneration

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

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

Blood-Brain Barrier Dysfunction and the Pathogenesis of Alzheimer’s Disease

(2017) et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Metformin ameliorates BSCB disruption by inhibiting neutrophil infiltration and MMP-9 expression but not direct TJ proteins expression regulation

(2017) Di Zhang et al.   JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

Astrocyte Transforming Growth Factor Beta 1 Protects Synapses against Aβ Oligomers in Alzheimer's Disease Model

(2017) Luan Pereira Diniz et al.   JOURNAL OF NEUROSCIENCE

Metformin Suppressed CXCL8 Expression and Cell Migration in HEK293/TLR4 Cell Line

(2017) Zhihui Xiao et al.   MEDIATORS OF INFLAMMATION

Metformin vs sulfonylurea use and risk of dementia in US veterans aged ≥65 years with diabetes

(2017) Ariela R. Orkaby et al.   NEUROLOGY

Clinical Neurology and Epidemiology of the Major Neurodegenerative Diseases

(2017) Michael G. Erkkinen et al.   Cold Spring Harbor Perspectives in Biology

Metformin inhibits esophageal squamous cell carcinoma-induced angiogenesis by suppressing JAK/STAT3 signaling pathway

(2017) Yi Yang et al.   Oncotarget

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

(2017) Shikha Prasad et al.   Redox Biology

Inflammation and NF-κB in Alzheimer's Disease and Diabetes

(2017) Ivica Granic et al.   JOURNAL OF ALZHEIMERS DISEASE

Metformin Attenuates Cognitive Impairments in Hypoxia–Ischemia Neonatal Rats via Improving Remyelination

(2016) Boxiang Qi et al.   CELLULAR AND MOLECULAR NEUROBIOLOGY

Unraveling Alzheimer’s: Making Sense of the Relationship between Diabetes and Alzheimer’s Disease1

(2016) Melissa A. Schilling   JOURNAL OF ALZHEIMERS DISEASE

Metformin promotes tau aggregation and exacerbates abnormal behavior in a mouse model of tauopathy

(2016) Erica Barini et al.   Molecular Neurodegeneration

Diabetes and Alzheimer’s disease crosstalk

(2016) David Baglietto-Vargas et al.   NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS

TNF-α stimulates MMP-3 production via PGE2 signalling through the NF-kB and p38 MAPK pathway in a murine cementoblast cell line

(2015) Neeracha Sanchavanakit et al.   ARCHIVES OF ORAL BIOLOGY

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

Endothelial LRP1 transports amyloid-β1–42 across the blood-brain barrier

(2015) Steffen E. Storck et al.   JOURNAL OF CLINICAL INVESTIGATION

The interleukin 1 alpha, interleukin 1 beta, interleukin 6 and alpha-2-macroglobulin serum levels in patients with early or late onset Alzheimer's disease, mild cognitive impairment or Parkinson's disease

(2015) Erdinç Dursun et al.   JOURNAL OF NEUROIMMUNOLOGY

Dehydroascorbic Acid Promotes Cell Death in Neurons Under Oxidative Stress: a Protective Role for Astrocytes

(2015) Andrea García-Krauss et al.   MOLECULAR NEUROBIOLOGY

Neutrophils promote Alzheimer's disease–like pathology and cognitive decline via LFA-1 integrin

(2015) Elena Zenaro et al.   NATURE MEDICINE

GLUT1 reductions exacerbate Alzheimer's disease vasculo-neuronal dysfunction and degeneration

(2015) Ethan A Winkler et al.   NATURE NEUROSCIENCE

Neutrophil Extracellular Trap Mitochondrial DNA and Its Autoantibody in Systemic Lupus Erythematosus and a Proof-of-Concept Trial of Metformin

(2015) Haiting Wang et al.   Arthritis & Rheumatology

Targeting Src-mediated Tyr216 phosphorylation and activation of GSK-3 in prostate cancer cells inhibit prostate cancer progression in vitro and in vivo

(2015) Anna Goc et al.   Oncotarget

Autophagy in microglia degrades extracellular β-amyloid fibrils and regulates the NLRP3 inflammasome

(2014) Mi-Hyang Cho et al.   Autophagy

Metformin Eased Cognitive Impairment Induced by Chronic L-methionine Administration: Potential Role of Oxidative Stress

(2014) Karem. Alzoubi et al.   Current Neuropharmacology

Neutrophils Mediate Blood–Spinal Cord Barrier Disruption in Demyelinating Neuroinflammatory Diseases

(2014) Benoit Aubé et al.   JOURNAL OF IMMUNOLOGY

Neutrophil contribution to spinal cord injury and repair

(2014) Virginie Neirinckx et al.   Journal of Neuroinflammation

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

(2014) Yanqun Liu et al.   Journal of Neuroinflammation

Metformin induces up-regulation of blood–brain barrier functions by activating AMP-activated protein kinase in rat brain microvascular endothelial cells

(2013) Fuyuko Takata et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

AMP-Activated Protein Kinase Regulates Endothelial Cell Angiotensin-Converting Enzyme Expression via p53 and the Post-Transcriptional Regulation of microRNA-143/145

(2013) Karin Kohlstedt et al.   CIRCULATION RESEARCH

Increased Risk of Cognitive Impairment in Patients With Diabetes Is Associated With Metformin

(2013) E. M. Moore et al.   DIABETES CARE

Blood–Brain Barrier Dysfunction as a Cause and Consequence of Alzheimer's Disease

(2013) Michelle A Erickson et al.   JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

Microglia-mediated neuroinflammation is an amplifier of virus-induced neuropathology

(2013) Jayasri Das Sarma   JOURNAL OF NEUROVIROLOGY

Metformin inhibits inflammatory response via AMPK–PTEN pathway in vascular smooth muscle cells

(2012) Sun Ae Kim et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Neuroprotection with metformin and thymoquinone against ethanol-induced apoptotic neurodegeneration in prenatal rat cortical neurons

(2012) Ikram Ullah et al.   BMC NEUROSCIENCE

A multimodal RAGE-specific inhibitor reduces amyloid β–mediated brain disorder in a mouse model of Alzheimer disease

(2012) Rashid Deane et al.   JOURNAL OF CLINICAL INVESTIGATION

Metformin, Other Antidiabetic Drugs, and Risk of Alzheimer's Disease: A Population-Based Case-Control Study

(2012) Patrick Imfeld et al.   JOURNAL OF THE AMERICAN GERIATRICS SOCIETY

Vascular β-amyloid and early astrocyte alterations impair cerebrovascular function and cerebral metabolism in transgenic arcAβ mice

(2011) Mario Merlini et al.   ACTA NEUROPATHOLOGICA

Ginsenoside Rg1 promotes nonamyloidgenic cleavage of APP via estrogen receptor signaling to MAPK/ERK and PI3K/Akt

(2011) Chun Shi et al.   BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS

Dysfunction of TGF-β1 signaling in Alzheimer’s disease: perspectives for neuroprotection

(2011) Filippo Caraci et al.   CELL AND TISSUE RESEARCH

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

(2011) Amit Gupta et al.   NEUROPHARMACOLOGY

Molecular mechanisms of neurodegeneration in Alzheimer's disease

(2010) L. Crews et al.   HUMAN MOLECULAR GENETICS

Transforming growth factor beta and soluble endoglin in the healthy senior and in Alzheimer’s disease patients

(2010) B. Juraskova et al.   Journal of Nutrition Health & Aging

Increased platelet GSK3B activity in patients with mild cognitive impairment and Alzheimer’s disease

(2010) Orestes V. Forlenza et al.   JOURNAL OF PSYCHIATRIC RESEARCH

IGF-1 Reduces BACE-1 Expression in PC12 Cells via Activation of PI3-K/Akt and MAPK/ERK1/2 Signaling Pathways

(2010) Hua Zhang et al.   NEUROCHEMICAL RESEARCH

Hydrogen sulfide reduces mRNA and protein levels of beta-site amyloid precursor protein cleaving enzyme 1 in PC12 cells

(2010) Hua Zhang et al.   NEUROCHEMISTRY INTERNATIONAL

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

Alzheimer's disease drug development and the problem of the blood-brain barrier

(2009) William M. Pardridge   Alzheimers & Dementia

PI3K inhibition causes the accumulation of ubiquitinated presenilin 1 without affecting the proteasome activity

(2009) Nobuhisa Aoyagi et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Degradation of Amyloid β Protein by Purified Myelin Basic Protein

(2009) Mei-Chen Liao et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Overexpression of Low-Density Lipoprotein Receptor in the Brain Markedly Inhibits Amyloid Deposition and Increases Extracellular Aβ Clearance

(2009) Jungsu Kim et al.   NEURON

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

Blood–brain barrier permeability in Alzheimer's disease: a case–control MRI study

(2009) John M. Starr et al.   PSYCHIATRY RESEARCH-NEUROIMAGING

Potential therapeutic targets of huperzine A for Alzheimer's disease and vascular dementia

(2008) Hai Yan Zhang et al.   CHEMICO-BIOLOGICAL INTERACTIONS

Metformin inhibits TNF-α-induced IκB kinase phosphorylation, IκB-α degradation and IL-6 production in endothelial cells through PI3K-dependent AMPK phosphorylation

(2008) Nan-Lan Huang et al.   INTERNATIONAL JOURNAL OF CARDIOLOGY

ATP-binding cassette transporter A1 (ABCA1) deficiency does not attenuate the brain-to-blood efflux transport of human amyloid-β peptide (1–40) at the blood–brain barrier

(2007) Shin-ichi Akanuma et al.   NEUROCHEMISTRY INTERNATIONAL