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MAR 11, 2020 10:30 AM PDT

Innate immunity in chronic neurodegeneration

Presented at: Neuroscience 2020
Sponsored by: NanoString Technologies
C.E. Credits: P.A.C.E. CE Florida CE
Speaker
  • Director of the Department of Neurodegenerative Diseases and Gerontopsychiatry at the University of Bonn, Germany
    Biography
      Michael Heneka completed his medical coursework at the University of Tübingen, Germany in 1996. He obtained his medical degree in 1998 at the Institute of Pharmacology and Toxicology of the University of Tübingen on the topic "The effect of polymerized hemoglobin on cardiovascular and renal parameters in septic shock." Thereafter he was a postdoc in the laboratory of Prof. DL Feinstein, at the University of Illinois at Chicago, Chicago, USA. In 2002 he passed the board examination in Neurology and qualified as a professor in Neurology in 2003 with a habilitation thesis entitled "Inflammatory mechanisms in Alzheimer's disease: characterization and development of therapeutic strategies" at the University of Bonn. He was offered a Fellowship in the Department of Neurosciences, Case Western Reserve University, Cleveland, USA, in the laboratory of Prof. K. Herrup and Prof. GE Landreth in 2004, after which he returned to Germany as a senior physician in the Department of Neurology at the University of Bonn. This was followed by a professorship (C3) for molecular neurology at the University of Münster (WWU) from 2004 to 2008. During this time he was head of the Department of Molecular Neuroscience and of the dementia clinic at the University Hospital MS. In 2008 he was appointed as Professor (W3) for Clinical Neurosciences at the Rheinische Friedrich-Wilhelms-Universität Bonn. Since 2010 Prof. Heneka has been the Neurological Director of the joint Memory Clinic of the Departments of Psychiatry and Neurology (Clinical Treatment and Research Center, KBFZ), University Hospital Bonn. Beyond his research, reviewer and teaching duties, Michael Heneka serves as head of the Clinical Research Unit 177 (DFG), is a board member of the BMBF Competence Network "Degenerative Dementias" (KNDD) and is a member of the BONFOR Commission. He is also the Organizing Chair of the biennial conference "Venusberg Meeting on Neuroinflammation". In 2011 he received the Christa Lorenz Award for ALS Research.

    Abstract

    The accumulation of neurotoxic amyloid beta peptides and/or neurofibrillary tangle formation are key pathological hallmarks of neurodegenerative diseases including but not limited to Alzheimer’s disease, frontotemporal dementia and multi-system atrophy. The brain has been considered as an immune-privileged organ, however, increasing evidence from translational, genetic, and pathological studies suggests that activation of distinct innate immune pathways are a third important disease hallmark which, once initiated, actively contributes to progression and chronicity of neurodegenerative disease.

    Microglia play a pivotal role in this immune response and are activated by binding of aggregated proteins or aberrant nucleic acids to pattern recognition receptors. This immune activation leads to the release of inflammatory mediators, but also distracts microglia cells from their physiological functions and tasks, including debris clearance and trophic factor support. NLRP3 inflammasome activation and release of ASC specks contribute to spreading of pathology and impair microglia clearance mechanisms, and together contribute to neuronal spine loss, neuronal degeneration, and ultimately to spatial memory deficits. In keeping with this immune hypothesis of neurodegeneration, inhibition of this and other immune pathways protect from neurodegeneration in cellular and murine models of neurodegenerative disease. Modulation of the microglia driven innate immune response at key signaling steps might therefore be protective and alter disease progression. However, the microglia are not a stable population, but have continuous turn over, most likely resulting in more than one generation of microglia being involved in disease progression.  Moreover their turnover is increased in response to neurodegeneration. Along with the regional diversity of microglia, these phenomena need to be understood in more detail prior to targeting innate immune mechanisms for therapeutic purposes.


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