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

Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain

(2020) Julia Marschallinger et al.   NATURE NEUROSCIENCE

TREM2 Regulates Microglial Cholesterol Metabolism upon Chronic Phagocytic Challenge

(2020) Alicia A. Nugent et al.   NEURON

Lysosome biology in autophagy

(2020) Willa Wen-You Yim et al.   Cell Discovery

Mechanism of Secondary Ganglioside and Lipid Accumulation in Lysosomal Disease

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

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

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

Alzheimer’s-associated PLCγ2 is a signaling node required for both TREM2 function and the inflammatory response in human microglia

(2020) Benjamin J. Andreone et al.   NATURE NEUROSCIENCE

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

(2020) Georg Werner et al.   EMBO REPORTS

Neurotoxic microglia promote TDP-43 proteinopathy in progranulin deficiency

(2020) Jiasheng Zhang et al.   NATURE

Emerging Microglia Biology Defines Novel Therapeutic Approaches for Alzheimer’s Disease

(2020) Joseph W. Lewcock et al.   NEURON

Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk

(2019) Iris E. Jansen et al.   NATURE GENETICS

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

Opposite microglial activation stages upon loss of PGRN or TREM2 result in reduced cerebral glucose metabolism

(2019) Julia K Götzl et al.   EMBO Molecular Medicine

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

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

(2019) Clarissa Valdez et al.   HUMAN MOLECULAR GENETICS

Intracellular cholesterol trafficking is dependent upon NPC2 interaction with lysobisphosphatidic acid

(2019) Leslie A McCauliff et al.   eLife

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

Murine knockin model for progranulin-deficient frontotemporal dementia with nonsense-mediated mRNA decay

(2018) Andrew D. Nguyen et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal fragments and unique lipid signatures

(2018) André M. Miranda et al.   Nature Communications

Brain Shuttle Antibody for Alzheimer’s Disease with Attenuated Peripheral Effector Function due to an Inverted Binding Mode

(2018) Felix Weber et al.   Cell Reports

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

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

Glucosylsphingosine Promotes α-Synuclein Pathology in Mutant GBA-Associated Parkinson's Disease

(2017) Yumiko V. Taguchi et al.   JOURNAL OF NEUROSCIENCE

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

Differentiation of human and murine induced pluripotent stem cells to microglia-like cells

(2017) Hetal Pandya et al.   NATURE NEUROSCIENCE

Progranulin, lysosomal regulation and neurodegenerative disease

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

Microglial NFκB-TNFα hyperactivation induces obsessive–compulsive behavior in mouse models of progranulin-deficient frontotemporal dementia

(2017) Grietje Krabbe et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

Lipidomic and Transcriptomic Basis of Lysosomal Dysfunction in Progranulin Deficiency

(2017) Bret M. Evers et al.   Cell Reports

Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation

(2016) Hansen Lui et al.   CELL

Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9

(2016) John G Doench et al.   NATURE BIOTECHNOLOGY

Neurofilament light chain: a biomarker for genetic frontotemporal dementia

(2016) Lieke H. Meeter et al.   Annals of Clinical and Translational Neurology

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

(2016) Jinlong Jian et al.   EBioMedicine

Progression of Behavioral and CNS Deficits in a Viable Murine Model of Chronic Neuronopathic Gaucher Disease

(2016) Mei Dai et al.   PLoS One

Strikingly Different Clinicopathological Phenotypes Determined by Progranulin-Mutation Dosage

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

Progranulin deficiency promotes neuroinflammation and neuron loss following toxin-induced injury

(2012) Lauren Herl Martens et al.   JOURNAL OF CLINICAL INVESTIGATION

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

Delayed inflammatory mRNA and protein expression after spinal cord injury

(2011) Kimberly R Byrnes et al.   Journal of Neuroinflammation

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

Brain progranulin expression in GRN-associated frontotemporal lobar degeneration

(2009) Alice S. Chen-Plotkin et al.   ACTA NEUROPATHOLOGICA

Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice

(2009) Fangfang Yin et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Divergent patterns of cytosolic TDP-43 and neuronal progranulin expression following axotomy: Implications for TDP-43 in the physiological response to neuronal injury

(2008) Katie Moisse et al.   BRAIN RESEARCH

Low plasma progranulin levels predict progranulin mutations in frontotemporal lobar degeneration

(2008) R. Ghidoni et al.   NEUROLOGY