Targeting complement in neurodegeneration: challenges, risks, and strategies

Article Chemistry, Medicinal

BBPpred: Sequence-Based Prediction of Blood-Brain Barrier Peptides with Feature Representation Learning and Logistic Regression

Ruyu Dai et al.

Summary: BBPpred is a computational method for predicting blood-brain barrier peptides that efficiently identifies informative features and shows promising performance on both training and independent test datasets.

JOURNAL OF CHEMICAL INFORMATION AND MODELING (2021)

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Article Neurosciences

Transplantation of human dental pulp stem cells compensates for striatal atrophy and modulates neuro-inflammation in 3-nitropropionic acid rat model of Huntington's disease

Neda Eskandari et al.

Summary: The study showed the potential neuroprotective effects of implantation of dental pulp stem cells (DPSCs) in a rat model of Huntington's disease, including enhanced motor skills, reduced striatum shrinkage, and inhibition of gliosis and microgliosis.

NEUROSCIENCE RESEARCH (2021)

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Review Neurosciences

An Outside-In and Inside-Out Consideration of Complement in the Multiple Sclerosis Brain: Lessons From Development and Neurodegenerative Diseases

B. Paul Morgan et al.

Summary: Research in the past 15 years has uncovered the significant role of complement in the central nervous system (CNS), impacting various processes such as cell migration, synaptic elimination during development, and damage to nerve cells in neurologic disorders and injury. Evidence suggests that complement production from CNS-resident cells, along with intracellular complement functions, may play a crucial role in shaping synaptic circuits and pathology within the brain.

FRONTIERS IN CELLULAR NEUROSCIENCE (2021)

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Review Biochemistry & Molecular Biology

The complement system in age-related macular degeneration

Angela Armento et al.

Summary: Age-related macular degeneration (AMD) is a complex disease with genetic, aging, and lifestyle factors all playing a role in its onset and progression. Therapeutic attempts targeting the complement system have not been successful, highlighting the complexity of AMD beyond genetic factors.

CELLULAR AND MOLECULAR LIFE SCIENCES (2021)

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Review Biotechnology & Applied Microbiology

Targeting the complement system in neuromyelitis optica spectrum disorder

Nithi Asavapanumas et al.

Summary: This review examines the immune mechanisms in AQP4-IgG seropositive NMOSD, including complement-dependent and complement-independent tissue injury. The discussion focuses on complement targets, such as complement proteins, regulators, anaphylatoxin receptors, and potential drug candidates.

EXPERT OPINION ON BIOLOGICAL THERAPY (2021)

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Review Pharmacology & Pharmacy

Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics

Peter Garred et al.

Summary: The complement system is the host's defense friend by protecting it from invading pathogens, promoting tissue repair, and maintaining homeostasis. Complement is a double-edged sword, since when dysregulated or overactivated it becomes the host's enemy, leading to tissue damage, organ failure, and, in worst case, death. A number of acute and chronic diseases are candidates for pharmacological treatment to avoid complement-dependent damage, ranging from the well established treatment for rare diseases to possible future treatment of large patient groups like the pandemic coronavirus disease 2019.

PHARMACOLOGICAL REVIEWS (2021)

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Article Genetics & Heredity

The Impact of Complement Genes on the Risk of Late-Onset Alzheimer's Disease

Sarah M. Carpanini et al.

Summary: Late-onset Alzheimer's disease is a neurodegenerative disease with uncertain etiology. Research suggests that complement genes may be associated with the risk of the disease, particularly CLU and CR1 genes, but further studies are needed for confirmation.

GENES (2021)

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Review Biochemistry & Molecular Biology

Brain Disposition of Antibody-Based Therapeutics: Dogma, Approaches and Perspectives

Aida Kouhi et al.

Summary: Monoclonal antibodies have high specificity and are being investigated for drug delivery to the CNS for neurological disease treatment, with the main challenge being the presence of the blood-brain barrier limiting drug uptake into the brain. Current research focuses on improving the physicochemical and biochemical properties of antibodies to enhance their uptake in the brain.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Immunology

Alpha-synuclein activates the classical complement pathway and mediates complement-dependent cell toxicity

Emil Gregersen et al.

Summary: The study demonstrates that alpha-synuclein can activate the classical complement pathway, leading to complement-dependent cellular toxicity, which can be rescued by complement inhibitors. There is also a trend for higher levels of C1q in the putamen of MSA patients, suggesting the involvement of the complement system in synucleinopathies.

JOURNAL OF NEUROINFLAMMATION (2021)

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News Item Multidisciplinary Sciences

LANDMARK ALZHEIMER'S DRUG APPROVAL CONFOUNDS RESEARCH COMMUNITY

Asher Mullard

NATURE (2021)

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Review Clinical Neurology

Convection-Enhanced Delivery and Principles of Extracellular Transport in the Brain

Amir H. Faraji et al.

Summary: This article focuses on the convection-enhanced delivery in stereotactic neurosurgery, highlighting the importance of understanding the biophysical properties of molecular transport in the extracellular space. By addressing current efforts and challenges, the article aims to further refine predictive models for advances in drug delivery techniques to the brain.

WORLD NEUROSURGERY (2021)

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Review Immunology

The Role of Complement in Synaptic Pruning and Neurodegeneration

Angela Gomez-Arboledas et al.

Summary: The complement system is essential for brain function, but inappropriate activation can lead to inflammation; Initial components C1q and C-3 play key roles in synaptic refinement, but excessive pruning may be harmful.

IMMUNOTARGETS AND THERAPY (2021)

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Article Neurosciences

Blood-spinal cord barrier leakage is independent of motor neuron pathology in ALS

Sarah Waters et al.

Summary: ALS is a fatal neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons. In ALS patients, there is evidence of blood-spinal cord barrier leakage during life, but the regions with the most severe barrier damage do not correlate with the areas of most abundant TDP-43 accumulation. This suggests that BSCB leakage and TDP-43 pathology are independent pathologies in ALS.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2021)

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Review Public, Environmental & Occupational Health

Estimated Prevalence and Incidence of Amyotrophic Lateral Sclerosis and SOD1 and C9orf72 Genetic Variants

Carolyn A. Brown et al.

Summary: This study estimated the prevalence and incidence of ALS and SOD1/C9orf72 ALS cases in 22 countries across Europe, North America, Latin America, and Asia. Significant heterogeneity in reported incidence and prevalence was observed within and between countries/geographic regions. The majority of SOD1 and C9orf72 ALS cases were found among those with sporadic ALS, indicating that the classification of familial ALS based on reported family history may not fully capture the genetic origin of ALS.

NEUROEPIDEMIOLOGY (2021)

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Article Clinical Neurology

Cerebrospinal fluid complement system biomarkers in demyelinating disease

Wioleta Milena Zelek et al.

MULTIPLE SCLEROSIS JOURNAL (2020)

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Article Immunology

Complement-dependent synapse loss and microgliosis in a mouse model of multiple sclerosis

Jennetta W. Hammond et al.

BRAIN BEHAVIOR AND IMMUNITY (2020)

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Review Immunology

Complement-Mediated Events in Alzheimer's Disease: Mechanisms and Potential Therapeutic Targets

Andrea J. Tenner

JOURNAL OF IMMUNOLOGY (2020)

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Article Multidisciplinary Sciences

The process of Lewy body formation, rather than simply α-synuclein fibrillization, is one of the major drivers of neurodegeneration

Anne-Laure Mahul-Mellier et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

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Review Geriatrics & Gerontology

Blood-Brain Barrier and Delivery of Protein and Gene Therapeutics to Brain

William M. Pardridge

FRONTIERS IN AGING NEUROSCIENCE (2020)

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Article Cell Biology

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

Mihalis S. Kariolis et al.

SCIENCE TRANSLATIONAL MEDICINE (2020)

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Review Immunology

The good, the bad, and the opportunities of the complement system in neurodegenerative disease

Nicole D. Schartz et al.

JOURNAL OF NEUROINFLAMMATION (2020)

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Article Physiology

Blood-Brain Barrier Leakage Is Increased in Parkinson's Disease

Sarah Al-Bachari et al.

FRONTIERS IN PHYSIOLOGY (2020)

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Article Immunology

Monoclonal Antibodies Capable of Inhibiting Complement Downstream of C5 in Multiple Species

Wioleta M. Zelek et al.

FRONTIERS IN IMMUNOLOGY (2020)

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Article Health Care Sciences & Services

Risk Analysis of Eculizumab-Related Meningococcal Disease in Japan Using the Japanese Adverse Drug Event Report Database

Yumi Matsumura

DRUG HEALTHCARE AND PATIENT SAFETY (2020)

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Review Immunology

Inflammation in Huntington's disease: A few new twists on an old tale

Priscila Aparecida Costa Valadao et al.

JOURNAL OF NEUROIMMUNOLOGY (2020)

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Article Clinical Neurology

Inflammatory biomarkers in Alzheimer's disease plasma

Angharad R. Morgan et al.

ALZHEIMERS & DEMENTIA (2019)

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Article Biochemistry & Molecular Biology

Systemic inflammation impairs microglial Aβ clearance through NLRP3 inflammasome

Dario Tejera et al.

EMBO JOURNAL (2019)

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Review Clinical Neurology

Cognitive Impairment in Neuromyelitis Optica Spectrum Disorders: A Review of Clinical and Neuroradiological Features

Frederike Cosima Oertel et al.

FRONTIERS IN NEUROLOGY (2019)

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Article Clinical Neurology

Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay

Liu Shi et al.

ALZHEIMERS & DEMENTIA (2019)

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Article Biochemistry & Molecular Biology

Compendium of current complement therapeutics

Wioleta M. Zelek et al.

MOLECULAR IMMUNOLOGY (2019)

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Article Biotechnology & Applied Microbiology

Recombinant expressing angiopep-2 fused anti-VEGF single chain Fab (scFab) could cross blood-brain barrier and target glioma

Xuemei Ji et al.

AMB EXPRESS (2019)

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Article Neurosciences

Water-exchange MRI detects subtle blood-brain barrier breakdown in Alzheimer's disease rats

Ben R. Dickie et al.

NEUROIMAGE (2019)

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Review Immunology

Therapeutic Inhibition of the Complement System in Diseases of the Central Nervous System

Sarah M. Carpanini et al.

FRONTIERS IN IMMUNOLOGY (2019)

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Article Biochemistry & Molecular Biology

Amyotrophic lateral sclerosis: The complement and inflammatory hypothesis

Anne-Lene Kjaeldgaard et al.

MOLECULAR IMMUNOLOGY (2018)

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Review Neurosciences

MRI measurements of Blood-Brain Barrier function in dementia: A review of recent studies

Rajikha Raja et al.

NEUROPHARMACOLOGY (2018)

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Review Medicine, Research & Experimental

Current Strategies for Brain Drug Delivery

Xiaowei Dong

THERANOSTICS (2018)

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Article Geriatrics & Gerontology

Low-grade systemic inflammation is associated with functional disability in elderly people affected by dementia

Carlo Cervellati et al.

GEROSCIENCE (2018)

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Article Clinical Neurology

Plasma complement biomarkers distinguish multiple sclerosis and neuromyelitis optica spectrum disorder

Svetlana Hakobyan et al.

MULTIPLE SCLEROSIS JOURNAL (2017)

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Article Medicine, Research & Experimental

Huntington's Disease: Mechanisms of Pathogenesis and Therapeutic Strategies

Maria Jimenez-Sanchez et al.

COLD SPRING HARBOR PERSPECTIVES IN MEDICINE (2017)

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Article Clinical Neurology

Plasma complement biomarkers distinguish multiple sclerosis and neuromyelitis optica spectrum disorder

Svetlana Hakobyan et al.

MULTIPLE SCLEROSIS JOURNAL (2017)

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Article Neurosciences

The Correlation between Inflammatory Biomarkers and Polygenic Risk Score in Alzheimer's Disease

Angharad R. Morgan et al.

JOURNAL OF ALZHEIMERS DISEASE (2017)

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Review Chemistry, Medicinal

Routes for Drug Translocation Across the Blood-Brain Barrier: Exploiting Peptides as Delivery Vectors

Mie Kristensen et al.

JOURNAL OF PHARMACEUTICAL SCIENCES (2017)

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Article Cell Biology

Complement C3 deficiency protects against neurodegeneration in aged plaque-rich APP/PS1 mice

Qiaoqiao Shi et al.

SCIENCE TRANSLATIONAL MEDICINE (2017)

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Review Oncology

Delivery of Biologics Across the Blood-Brain Barrier with Molecular Trojan Horse Technology

William M. Pardridge

BIODRUGS (2017)

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Article Biochemistry & Molecular Biology

Cationization increases brain distribution of an amyloid-beta protofibril selective F(ab')2 fragment

Stina Syvanen et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2017)

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Review Immunology

Inflammation in Alzheimer's disease: Lessons learned from microglia-depletion models

Elizabeth E. Spangenberg et al.

BRAIN BEHAVIOR AND IMMUNITY (2017)

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Review Chemistry, Multidisciplinary

Blood-brain barrier shuttle peptides: an emerging paradigm for brain delivery

Benjami Oller-Salvia et al.

CHEMICAL SOCIETY REVIEWS (2016)

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Article Emergency Medicine

Diagnosis and Treatment of Central Nervous System Infections in the Emergency Department

Maia Dorsett et al.

EMERGENCY MEDICINE CLINICS OF NORTH AMERICA (2016)

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Article Immunology

The membrane attack complex as an inflammatory trigger

B. Paul Morgan

IMMUNOBIOLOGY (2016)

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Article Immunology

Complement is activated in progressive multiple sclerosis cortical grey matter lesions

Lewis M. Watkins et al.

JOURNAL OF NEUROINFLAMMATION (2016)

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Article Multidisciplinary Sciences

Complement and microglia mediate early synapse loss in Alzheimer mouse models

Soyon Hong et al.

SCIENCE (2016)

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Article Clinical Neurology

Complement C1q-C3-associated synaptic changes in multiple sclerosis hippocampus

Iliana Michailidou et al.

ANNALS OF NEUROLOGY (2015)

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Review Immunology

Systemic inflammation and microglial activation: systematic review of animal experiments

Inge C. M. Hoogland et al.

JOURNAL OF NEUROINFLAMMATION (2015)

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Review Biotechnology & Applied Microbiology

Complement, a target for therapy in inflammatory and degenerative diseases

B. Paul Morgan et al.

NATURE REVIEWS DRUG DISCOVERY (2015)

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Article Geriatrics & Gerontology

Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases

Claudio Franceschi et al.

JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES (2014)

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Article Neurosciences

Complement activation in multiple sclerosis plaques: an immunohistochemical analysis

Gillian Ingram et al.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2014)

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Article Genetics & Heredity

Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease

Jean-Charles Lambert et al.

NATURE GENETICS (2013)

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Review Immunology

Microglia and macrophages of the central nervous system: the contribution of microglia priming and systemic inflammation to chronic neurodegeneration

V. Hugh Perry et al.

SEMINARS IN IMMUNOPATHOLOGY (2013)

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Review Immunology

Complement dysregulation and disease: From genes and proteins to diagnostics and drugs

Santiago Rodriguez de Cordoba et al.

IMMUNOBIOLOGY (2012)

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Review Clinical Neurology

Aquaporin 4 and neuromyelitis optica

Marios C. Papadopoulos et al.

LANCET NEUROLOGY (2012)

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Article Clinical Neurology

Systemic complement profiling in multiple sclerosis as a biomarker of disease state

G. Ingram et al.

MULTIPLE SCLEROSIS JOURNAL (2012)

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Article Neurosciences

Targeted inhibition of complement using complement receptor 2-conjugated inhibitors attenuates EAE

Xianzhen Hu et al.

NEUROSCIENCE LETTERS (2012)

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Article Immunology

Complement upregulation and activation on motor neurons and neuromuscular junction in the SOD1 G93A mouse model of familial amyotrophic lateral sclerosis

Bianca Heurich et al.

JOURNAL OF NEUROIMMUNOLOGY (2011)

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Review Biochemistry & Molecular Biology

Complement in the brain

Robert Veerhuis et al.

MOLECULAR IMMUNOLOGY (2011)

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Article Neurosciences

Innate and adaptive immunity in amyotrophic lateral sclerosis: Evidence of complement activation

M. Sta et al.

NEUROBIOLOGY OF DISEASE (2011)

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Article Cell Biology

A Therapeutic Antibody Targeting BACE1 Inhibits Amyloid-β Production in Vivo

Jasvinder K. Atwal et al.

SCIENCE TRANSLATIONAL MEDICINE (2011)

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Article Cell Biology

Boosting Brain Uptake of a Therapeutic Antibody by Reducing Its Affinity for a Transcytosis Target

Y. Joy Yu et al.

SCIENCE TRANSLATIONAL MEDICINE (2011)

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Review Microbiology

Penetration of Drugs through the Blood-Cerebrospinal Fluid/Blood-Brain Barrier for Treatment of Central Nervous System Infections

Roland Nau et al.

CLINICAL MICROBIOLOGY REVIEWS (2010)

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Article Neurosciences

Involvement of Immune Response in the Pathogenesis of Amyotrophic Lateral Sclerosis: A Therapeutic Opportunity?

A. Calvo et al.

CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS (2010)

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Article Clinical Neurology

Immunoglobulins and Complement in Postmortem Multiple Sclerosis Tissue

Michael H. Barnett et al.

ANNALS OF NEUROLOGY (2009)

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Article Genetics & Heredity

Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease

Jean-Charles Lambert et al.

NATURE GENETICS (2009)

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Article Immunology

The Complement Factor C5a Contributes to Pathology in a Rat Model of Amyotrophic Lateral Sclerosis

Trent M. Woodruff et al.

JOURNAL OF IMMUNOLOGY (2008)

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Article Neurosciences

Complement C3 deficiency leads to accelerated amyloid β plaque deposition and neurodegeneration and modulation of the microglia/macrophage phenotype in amyloid precursor protein transgenic mice

Marcel Maier et al.

JOURNAL OF NEUROSCIENCE (2008)

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Article Immunology

Complement activation in the Parkinson's disease substantia nigra: an immunocytochemical study

David A. Loeffler et al.

JOURNAL OF NEUROINFLAMMATION (2006)

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Article Geriatrics & Gerontology

Inflammation, the complement system and the diseases of aging

EG McGeer et al.

NEUROBIOLOGY OF AGING (2005)

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Article Medicine, General & Internal

A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis

VA Lennon et al.

LANCET (2004)

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Article Biochemistry & Molecular Biology

High transcytosis of melanotransferrin (P97) across the blood brain barrier

M Demeule et al.

JOURNAL OF NEUROCHEMISTRY (2002)

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Article Clinical Neurology

The overlap of amyotrophic lateral sclerosis and frontotemporal dementia

C Lomen-Hoerth et al.

NEUROLOGY (2002)

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Article Immunology

β-amyloid fibrils activate the C1 complex of complement under physiological conditions:: Evidence for a binding site for Aβ on the C1q globular regions

P Tacnet-Delorme et al.

JOURNAL OF IMMUNOLOGY (2001)

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Review Pharmacology & Pharmacy

Advances in osmotic opening of the blood-brain barrier to enhance CNS chemotherapy

SI Rapoport

EXPERT OPINION ON INVESTIGATIONAL DRUGS (2001)

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Targeting complement in neurodegeneration: challenges, risks, and strategies

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