Lysosomal functions of progranulin and implications for treatment of frontotemporal dementia

Loss of TREM2 rescues hyperactivation of microglia, but not lysosomal deficits and neurotoxicity in models of progranulin deficiency

(2022) Anika Reifschneider et al.   EMBO JOURNAL

Differential regulation of progranulin derived granulin peptides

(2022) Tingting Zhang et al.   Molecular Neurodegeneration

Progranulin as a therapeutic target in neurodegenerative diseases

(2022) Herve Rhinn et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Adeno-Associated Virus Toolkit to Target Diverse Brain Cells

(2022) Rosemary C. Challis et al.   Annual Review of Neuroscience

Neuroinflammation in Gaucher disease, neuronal ceroid lipofuscinosis, and commonalities with Parkinson’s disease

(2022) Laetitia Francelle et al.   BRAIN RESEARCH

Homotypic fibrillization of TMEM106B across diverse neurodegenerative diseases

(2022) Andrew Chang et al.   CELL

Age-dependent formation of TMEM106B amyloid filaments in human brains

(2022) Manuel Schweighauser et al.   NATURE

Amyloid fibrils in FTLD-TDP are composed of TMEM106B and not TDP-43

(2022) Yi Xiao Jiang et al.   NATURE

New insights into the genetic etiology of Alzheimer’s disease and related dementias

(2022) Céline Bellenguez et al.   NATURE GENETICS

Small molecule C381 targets the lysosome to reduce inflammation and ameliorate disease in models of neurodegeneration

(2022) Ryan T. Vest et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Progranulin-derived granulin E and lysosome membrane protein CD68 interact to reciprocally regulate their protein homeostasis

(2022) Mariela Nunez Santos et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia

(2022) Dan Xia et al.   Molecular Neurodegeneration

Deficiency of the frontotemporal dementia gene GRN results in gangliosidosis

(2022) Sebastian Boland et al.   Nature Communications

Anti-sortilin1 Antibody Up-Regulates Progranulin via Sortilin1 Down-Regulation

(2021) Shuuichi Miyakawa et al.   Frontiers in Neuroscience

Rescue of a lysosomal storage disorder caused by Grn loss of function with a brain penetrant progranulin biologic

(2021) Todd Logan et al.   CELL

Processing of progranulin into granulins involves multiple lysosomal proteases and is affected in frontotemporal lobar degeneration

(2021) Swetha Mohan et al.   Molecular Neurodegeneration

Microglial lysosome dysfunction contributes to white matter pathology and TDP-43 proteinopathy in GRN-associated FTD

(2021) Yanwei Wu et al.   Cell Reports

Tweaking Progranulin Expression: Therapeutic Avenues and Opportunities

(2021) Joke Terryn et al.   Frontiers in Molecular Neuroscience

New insights and therapeutic opportunities for progranulin-deficient frontotemporal dementia

(2021) Sadaf Amin et al.   CURRENT OPINION IN NEUROBIOLOGY

Sortilin regulates blood–brain barrier integrity

(2021) Andrea E. Toth et al.   FEBS Journal

Efficient progranulin exit from the ER requires its interaction with prosaposin, a Surf4 cargo

(2021) Swathi Devireddy et al.   JOURNAL OF CELL BIOLOGY

Effect of the Histone Deacetylase Inhibitor FRM-0334 on Progranulin Levels in Patients With Progranulin Gene Haploinsufficiency

(2021) Peter A. Ljubenkov et al.   JAMA Network Open

Progranulin as a Potential Therapeutic Target in Immune-Mediated Diseases

(2021) Yue-Jiao Lan et al.   Journal of Inflammation Research

TREM2 Regulates Microglial Cholesterol Metabolism upon Chronic Phagocytic Challenge

(2020) Alicia A. Nugent et al.   NEURON

Mechanism of Secondary Ganglioside and Lipid Accumulation in Lysosomal Disease

(2020) Bernadette Breiden et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Premature termination codon readthrough upregulates progranulin expression and improves lysosomal function in preclinical models of GRN deficiency

(2020) Jonathan Frew et al.   Molecular Neurodegeneration

Brain delivery of therapeutic proteins using an Fc fragment blood-brain barrier transport vehicle in mice and monkeys

(2020) Mihalis S. Kariolis et al.   Science Translational Medicine

Brain delivery and activity of a lysosomal enzyme using a blood-brain barrier transport vehicle in mice

(2020) Julie C. Ullman et al.   Science Translational Medicine

The FTLD Risk Factor TMEM106B Regulates the Transport of Lysosomes at the Axon Initial Segment of Motoneurons

(2020) Patrick Lüningschrör et al.   Cell Reports

Loss of TMEM106B leads to myelination deficits: implications for frontotemporal dementia treatment strategies

(2020) Xiaolai Zhou et al.   BRAIN

Loss of TMEM 106B and PGRN leads to severe lysosomal abnormalities and neurodegeneration in mice

(2020) Tuancheng Feng et al.   EMBO REPORTS

Loss of Tmem106b exacerbates FTLD pathologies and causes motor deficits in progranulin‐deficient mice

(2020) Xiaolai Zhou et al.   EMBO REPORTS

Discovery of small molecules that normalize the transcriptome and enhance cysteine cathepsin activity in progranulin-deficient microglia

(2020) Maria A. Telpoukhovskaia et al.   Scientific Reports

Loss of TMEM 106B potentiates lysosomal and FTLD ‐like pathology in progranulin‐deficient mice

(2020) Georg Werner et al.   EMBO REPORTS

Adeno-Associated Virus-Induced Dorsal Root Ganglion Pathology

(2020) Juliette Hordeaux et al.   HUMAN GENE THERAPY

Neurotoxic microglia promote TDP-43 proteinopathy in progranulin deficiency

(2020) Jiasheng Zhang et al.   NATURE

Pro-cathepsin D, Prosaposin, and Progranulin: Lysosomal Networks in Parkinsonism

(2020) Nahid Tayebi et al.   TRENDS IN MOLECULAR MEDICINE

Adeno‐associated virus serotype 1‐based gene therapy for FTD caused by GRN mutations

(2020) Christian Hinderer et al.   Annals of Clinical and Translational Neurology

Network analysis of the progranulin-deficient mouse brain proteome reveals pathogenic mechanisms shared in human frontotemporal dementia caused by GRN mutations

(2020) Meixiang Huang et al.   Acta Neuropathologica Communications

Balancing neurotrophin pathway and sortilin function: Its role in human disease

(2020) Minnatallah Al-Yozbaki et al.   BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER

Are granulins copper sequestering proteins?

(2020) Anukool A. Bhopatkar et al.   PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS

Transcytosis to Cross the Blood Brain Barrier, New Advancements and Challenges

(2019) Victor M. Pulgar   Frontiers in Neuroscience

Progranulin Stimulates the In Vitro Maturation of Pro-Cathepsin D at Acidic pH

(2019) Victoria J. Butler et al.   JOURNAL OF MOLECULAR BIOLOGY

Multi-Granulin Domain Peptides Bind to Pro-Cathepsin D and Stimulate Its Enzymatic Activity More Effectively Than Progranulin in Vitro

(2019) Victoria J. Butler et al.   BIOCHEMISTRY

Lysosomal Glycosphingolipid Storage Diseases

(2019) Bernadette Breiden et al.   Annual Review of Biochemistry

Progranulin deficiency leads to reduced glucocerebrosidase activity

(2019) Xiaolai Zhou et al.   PLoS One

Repair or Lysophagy: Dealing with Damaged Lysosomes

(2019) Chrisovalantis Papadopoulos et al.   JOURNAL OF MOLECULAR BIOLOGY

AAV-PHP.B Administration Results in a Differential Pattern of CNS Biodistribution in Non-human Primates Compared with Mice

(2019) William A. Liguore et al.   MOLECULAR THERAPY

Progranulin mutations result in impaired processing of prosaposin and reduced glucocerebrosidase activity

(2019) Clarissa Valdez et al.   HUMAN MOLECULAR GENETICS

Glycosphingolipids and lysosomal storage disorders as illustrated by gaucher disease

(2019) Johannes M.F.G. Aerts et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

(2019) Mike A Nalls et al.   LANCET NEUROLOGY

Life in the lumen: The multivesicular endosome

(2019) Jean Gruenberg   TRAFFIC

Impaired β-glucocerebrosidase activity and processing in frontotemporal dementia due to progranulin mutations

(2019) Andrew E. Arrant et al.   Acta Neuropathologica Communications

The lysosomal function of progranulin, a guardian against neurodegeneration

(2018) Daniel H. Paushter et al.   ACTA NEUROPATHOLOGICA

Progranulin Gene Therapy Improves Lysosomal Dysfunction and Microglial Pathology Associated with Frontotemporal Dementia and Neuronal Ceroid Lipofuscinosis

(2018) Andrew E. Arrant et al.   JOURNAL OF NEUROSCIENCE

Rare nonsynonymous variants in SORT1 are associated with increased risk for frontotemporal dementia

(2018) Stéphanie Philtjens et al.   NEUROBIOLOGY OF AGING

Triggered recruitment of ESCRT machinery promotes endolysosomal repair

(2018) Michael L. Skowyra et al.   SCIENCE

AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease

(2018) Jonathan B. Rosenberg et al.   Human Gene Therapy Clinical Development

Early lysosomal maturation deficits in microglia triggers enhanced lysosomal activity in other brain cells of progranulin knockout mice

(2018) Julia K. Götzl et al.   Molecular Neurodegeneration

Intracellular transport and regulation of transcytosis across the blood–brain barrier

(2018) Roberto Villaseñor et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

AAV-Mediated Progranulin Delivery to a Mouse Model of Progranulin Deficiency Causes T Cell-Mediated Toxicity

(2018) Defne A. Amado et al.   MOLECULAR THERAPY

Kinetics and MR-Based Monitoring of AAV9 Vector Delivery into Cerebrospinal Fluid of Nonhuman Primates

(2018) Kousaku Ohno et al.   Molecular Therapy-Methods & Clinical Development

Progranulin-mediated deficiency of cathepsin D results in FTD and NCL-like phenotypes in neurons derived from FTD patients

(2017) Clarissa Valdez et al.   HUMAN MOLECULAR GENETICS

Progranulin functions as a cathepsin D chaperone to stimulate axonal outgrowth in vivo

(2017) Sander Beel et al.   HUMAN MOLECULAR GENETICS

Lipids regulate the hydrolysis of membrane bound glucosylceramide by lysosomal β-glucocerebrosidase

(2017) Misbaudeen Abdul-Hammed et al.   JOURNAL OF LIPID RESEARCH

The interaction between progranulin and prosaposin is mediated by granulins and the linker region between saposin B and C

(2017) Xiaolai Zhou et al.   JOURNAL OF NEUROCHEMISTRY

Intrathecal antibody distribution in the rat brain: surface diffusion, perivascular transport and osmotic enhancement of delivery

(2017) Michelle E. Pizzo et al.   JOURNAL OF PHYSIOLOGY-LONDON

The lysosomal protein cathepsin L is a progranulin protease

(2017) Chris W. Lee et al.   Molecular Neurodegeneration

Lysosomal processing of progranulin

(2017) Xiaolai Zhou et al.   Molecular Neurodegeneration

Emptying the stores: lysosomal diseases and therapeutic strategies

(2017) Frances M. Platt   NATURE REVIEWS DRUG DISCOVERY

Progranulin, lysosomal regulation and neurodegenerative disease

(2017) Aimee W. Kao et al.   NATURE REVIEWS NEUROSCIENCE

Individuals with progranulin haploinsufficiency exhibit features of neuronal ceroid lipofuscinosis

(2017) Michael E. Ward et al.   Science Translational Medicine

Modifiers of GRN -Associated Frontotemporal Lobar Degeneration

(2017) Eline Wauters et al.   TRENDS IN MOLECULAR MEDICINE

Impaired prosaposin lysosomal trafficking in frontotemporal lobar degeneration due to progranulin mutations

(2017) Xiaolai Zhou et al.   Nature Communications

Differential Aging Analysis in Human Cerebral Cortex Identifies Variants in TMEM106B and GRN that Regulate Aging Phenotypes

(2017) Herve Rhinn et al.   Cell Systems

Trehalose upregulates progranulin expression in human and mouse models of GRN haploinsufficiency: a novel therapeutic lead to treat frontotemporal dementia

(2016) Christopher J. Holler et al.   Molecular Neurodegeneration

Prosaposin is a regulator of progranulin levels and oligomerization

(2016) Alexandra M. Nicholson et al.   Nature Communications

Cerebellomedullary Cistern Delivery for AAV-Based Gene Therapy: A Technical Note for Nonhuman Primates

(2016) Lluis Samaranch et al.   Human Gene Therapy Methods

Progranulin Recruits HSP70 to β-Glucocerebrosidase and Is Therapeutic Against Gaucher Disease

(2016) Jinlong Jian et al.   EBioMedicine

Association Between Progranulin and Gaucher Disease

(2016) Jinlong Jian et al.   EBioMedicine

Prosaposin facilitates sortilin-independent lysosomal trafficking of progranulin

(2015) Xiaolai Zhou et al.   JOURNAL OF CELL BIOLOGY

The Evolution of the Secreted Regulatory Protein Progranulin

(2015) Roger G. E. Palfree et al.   PLoS One

Transferrin receptor (TfR) trafficking determines brain uptake of TfR antibody affinity variants

(2014) Nga Bien-Ly et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Progranulin protein levels are differently regulated in plasma and CSF

(2014) A. M. Nicholson et al.   NEUROLOGY

Progranulin in neurodegenerative disease

(2014) Terri L. Petkau et al.   TRENDS IN NEUROSCIENCES

Possible involvement of lysosomal dysfunction in pathological changes of the brain in aged progranulin-deficient mice

(2014) Yoshinori Tanaka et al.   Acta Neuropathologica Communications

Brain Bioavailability of Human Intravenous Immunoglobulin and its Transport through the Murine Blood–Brain Barrier

(2013) Isabelle St-Amour et al.   JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

Promoter DNA methylation regulates progranulin expression and is altered in FTLD

(2013) Julia Banzhaf-Strathmann et al.   Acta Neuropathologica Communications

Strikingly Different Clinicopathological Phenotypes Determined by Progranulin-Mutation Dosage

(2012) Katherine R. Smith et al.   AMERICAN JOURNAL OF HUMAN GENETICS

Membrane Orientation and Subcellular Localization of Transmembrane Protein 106B (TMEM106B), a Major Risk Factor for Frontotemporal Lobar Degeneration

(2012) Christina M. Lang et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Exacerbated inflammatory responses related to activated microglia after traumatic brain injury in progranulin-deficient mice

(2012) Y. Tanaka et al.   NEUROSCIENCE

Association of TMEM106B Gene Polymorphism With Age at Onset in Granulin Mutation Carriers and Plasma Granulin Protein Levels

(2011) Carlos Cruchaga et al.   ARCHIVES OF NEUROLOGY

Progranulin, a Glycoprotein Deficient in Frontotemporal Dementia, Is a Novel Substrate of Several Protein Disulfide Isomerase Family Proteins

(2011) Sandra Almeida et al.   PLoS One

rs5848 polymorphism and serum progranulin level

(2010) Ging-Yuek R. Hsiung et al.   JOURNAL OF THE NEUROLOGICAL SCIENCES

From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus

(2010) Kiran Musunuru et al.   NATURE

Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions

(2010) Vivianna M Van Deerlin et al.   NATURE GENETICS

TMEM106B regulates progranulin levels and the penetrance of FTLD in GRN mutation carriers

(2010) N. Finch et al.   NEUROLOGY

Sortilin-Mediated Endocytosis Determines Levels of the Frontotemporal Dementia Protein, Progranulin

(2010) Fenghua Hu et al.   NEURON

Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia

(2008) Rosa Rademakers et al.   HUMAN MOLECULAR GENETICS