Abstract
Low-density lipoprotein receptor related protein-1 (LRP) is a member of the low-density lipoprotein (LDL) receptor family which has been linked to Alzheimers disease (AD) by biochemical and genetic evidence. Levels of neurotoxic amyloid β-peptide (Aβ) in the brain are elevated in AD contributing to the disease process and neuropathology. Faulty Aβ clearance from the brain appears to mediate focal Aβ accumulations in AD. Central and peripheral production of Aβ from Aβ-precursor protein (APP), transport of peripheral Aβ into the brain across the blood-brain barrier (BBB) via receptor for advanced glycation end products (RAGE), enzymatic Aβ degradation, Aβ oligomerization and aggregation, neuroinflammatory changes and microglia activation, and Aβ elimination from brain across the BBB by cell surface LRP; all may control brain Aβ levels. Recently, we have shown that a soluble form of LRP (sLRP) binds 70 to 90 % of plasma Aβ, preventing its access to the brain. In AD individuals, the levels of LRP at the BBB are reduced, as are levels of Aβ binding to sLRP in plasma. This, in turn, may increase Aβ brain levels through a decreased efflux of brain Aβ at the BBB and/or reduced sequestration of plasma Aβ associated with re-entry of free Aβ into the brain via RAGE. Thus, therapies which increase LRP expression at the BBB and/or enhance the peripheral Aβ “sink” activity of sLRP, hold potential to control brain Aβ accumulations, neuroinflammation and cerebral blood flow reductions in AD.
Keywords: LRP, sLRP, blood-brain barrier, Alzheimer's disease, Aβ clearance
Current Pharmaceutical Design
Title: The Role of the Cell Surface LRP and Soluble LRP in Blood-Brain Barrier Aβ Clearance in Alzheimers Disease
Volume: 14 Issue: 16
Author(s): R. Deane, A. Sagare and B. V. Zlokovic
Affiliation:
Keywords: LRP, sLRP, blood-brain barrier, Alzheimer's disease, Aβ clearance
Abstract: Low-density lipoprotein receptor related protein-1 (LRP) is a member of the low-density lipoprotein (LDL) receptor family which has been linked to Alzheimers disease (AD) by biochemical and genetic evidence. Levels of neurotoxic amyloid β-peptide (Aβ) in the brain are elevated in AD contributing to the disease process and neuropathology. Faulty Aβ clearance from the brain appears to mediate focal Aβ accumulations in AD. Central and peripheral production of Aβ from Aβ-precursor protein (APP), transport of peripheral Aβ into the brain across the blood-brain barrier (BBB) via receptor for advanced glycation end products (RAGE), enzymatic Aβ degradation, Aβ oligomerization and aggregation, neuroinflammatory changes and microglia activation, and Aβ elimination from brain across the BBB by cell surface LRP; all may control brain Aβ levels. Recently, we have shown that a soluble form of LRP (sLRP) binds 70 to 90 % of plasma Aβ, preventing its access to the brain. In AD individuals, the levels of LRP at the BBB are reduced, as are levels of Aβ binding to sLRP in plasma. This, in turn, may increase Aβ brain levels through a decreased efflux of brain Aβ at the BBB and/or reduced sequestration of plasma Aβ associated with re-entry of free Aβ into the brain via RAGE. Thus, therapies which increase LRP expression at the BBB and/or enhance the peripheral Aβ “sink” activity of sLRP, hold potential to control brain Aβ accumulations, neuroinflammation and cerebral blood flow reductions in AD.
Export Options
About this article
Cite this article as:
Deane R., Sagare A. and Zlokovic V. B., The Role of the Cell Surface LRP and Soluble LRP in Blood-Brain Barrier Aβ Clearance in Alzheimers Disease, Current Pharmaceutical Design 2008; 14 (16) . https://dx.doi.org/10.2174/138161208784705487
DOI https://dx.doi.org/10.2174/138161208784705487 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Role of Angiogenesis Inhibitors in Colorectal Cancer: Sensitive and Insensitive Tumors
Current Cancer Drug Targets Beneficial Effects of Vildagliptin on Metabolic Parameters in Patients with Type 2 Diabetes
Endocrine, Metabolic & Immune Disorders - Drug Targets Fc Receptors as Potential Targets for the Treatment of Allergy, Autoimmune Disease and Cancer
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Pharmacological Pre- and Post- Conditioning Agents: Reperfusion-Injury of the Heart Revisited
Mini-Reviews in Medicinal Chemistry Modulation of Plasma Non Enzimatic Antioxidant Capacity (NEAC) by Plant Foods: the Role of Polyphenol
Current Topics in Medicinal Chemistry The Importance of Reendothelialization After Arterial Injury
Current Pharmaceutical Design Cardiovascular Disease in the Rheumatic Diseases: How Systemic Inflammation May Contribute to Atherogenesis
Current Rheumatology Reviews The Triad: Erectile Dysfunction - Endothelial Dysfunction - Cardiovascular Disease
Current Pharmaceutical Design Q Fever Endocarditis
Infectious Disorders - Drug Targets Acute Hemorrhagic Edema of Infancy: A Diagnostic Challenge for the General Pediatrician
Current Pediatric Reviews ACE and ACE2 in Inflammation: A Tale of Two Enzymes
Inflammation & Allergy - Drug Targets (Discontinued) Epigenetic Mechanisms and Kidney Diseases
Current Medicinal Chemistry Pathologic Findings of Autoimmune Pancreatitis and IgG4-Related Disease
Current Immunology Reviews (Discontinued) Editorial [Hot Topic: The Eye in Rheumatological Disease (Guest Editors: Sue Lightman and Simon Taylor)]
Current Rheumatology Reviews Transcranial Doppler Ultrasonography: Current Status
Current Medical Imaging Combination of Captopril with Gliclazide Decreases Vascular and Renal Complications and Improves Glycemic Control in Rats with Streptozotocin- Induced Diabetes Mellitus
Endocrine, Metabolic & Immune Disorders - Drug Targets Improved Lipid Target Level Attainment in Patients with Peripheral Artery Disease
Current Vascular Pharmacology Effects Of Glycoprotein IIb/IIIa Antagonists: Anti Platelet Aggregation And Beyond
Current Drug Metabolism The Biology and Therapeutic Potential of the DDAH/ADMA Pathway
Current Pharmaceutical Design Pathophysiology of Atherosclerosis: The Role of Inflammation
Current Pharmaceutical Design