DATE: November 19, 2019
TIME: 10:00am PST
Microglial cells are the resident innate immune cells of the central nervous system (CNS) and are responsible for regulating inflammatory activation in response to both physiological and pathological immune perturbations. The mechanisms that fully control and dictate the nature of an inflammatory response in the CNS are still poorly understood. We have recently identified a novel pathway where components of the canonical autophagy machinery function to conjugate the microtubule-associated protein LC3 to endosomal membranes, a process we have termed LC3-associated endocytosis (LANDO). We further identified that abrogation of LANDO in microglial cells promotes pro-inflammatory cytokine production in vitro. To characterize LANDO and its role in immune regulation in the CNS, we utilized a well-established model of neuroinflammation induced by β-amyloid deposition. We found that mice lacking LANDO but not canonical autophagy in either the myeloid compartment or specifically in microglia, have a robust increase in pro-inflammatory cytokine production in the hippocampus and have increased levels of neurotoxic β-amyloid accumulation. This inflammation and β-amyloid deposition led to reactive microgliosis and hyperphosphorylation of tau, a protein that is vital to neuronal structure and function. As a consequence, LANDO-deficient Alzheimer’s Disease mice have increased neurodegeneration, resulting in impaired neuronal signaling and consequential behavioral and memory deficits. Mechanistically, β-amyloid is internalized by microglial cells through receptor-mediated endocytosis using a variety of surface receptors including Trem2 and CD36. We further identified that LANDO-deficiency not only alters immune activation upon endocytosis of β-amyloid, but results in impaired receptor recycling and extracellular β-amyloid accumulation. Exacerbation of β-amyloid accumulation further contributes to increased neuroinflammation. Together, our data support a protective role for LANDO in microglial cells of the CNS in neurodegenerative pathologies resulting from amyloid deposition.
Learning Objectives:
Webinars will be available for unlimited on-demand viewing after live event.
LabRoots is approved as a provider of continuing education programs in the clinical laboratory sciences by the ASCLS P.A.C.E. ® Program. By attending this webinar, you can earn 1 Continuing Education credit once you have viewed the webinar in its entirety.
Molecular Biology
Cell Biology
Immunology
Neuroscience
Cancer Research
Biochemistry
Biomarkers
Cell Culture
Biotechnology
Genetics
Molecular Diagnostics
Gene Expression
Clinical Research
Cancer Therapeutics
Microbiology
North America61%
Europe22%
Asia12%
South America3%
Africa1%
Email Promotions66%
Website Visitors27%
WAVE Newsletter Promotion3%
Other3%
Educator/Faculty17%
Student15%
Research Scientist14%
Executive9%
Scientist9%
Post Doc8%
Medical Laboratory Technician6%
Facility/Department Manager6%
Lab Management5%
Medical Doctor/Specialist5%
Clinical Laboratory Scientist3%
Biologist2%
Chemist1%
Academic Institution37%
Clinical Laboratory8%
Hospital7%
Biotech Company7%
Research Institute6%
Medical School6%
Government5%
Pharmaceutical Company4%
Life Science Company2%
Medical Center2%
Non-Profit Organization2%
Consultant2%
Diagnostic Company1%
Independent Laboratories1%
Other4%