AUG 23, 2023 10:00 AM PDT

Emerging role of neuroinflammation in C9orf72-ALS

Sponsored by: Miltenyi Biotec
  • Deepti Lall, PhD

    Project Scientist, Cedars-Sinai Board of Governors Regenerative Medicine Institute

Event Date & Time
Date: August 23, 2023
Time: 10:00 AM (PST), 1:00 PM (EST), 7:00 PM (CET)
C9orf72 repeat expansions cause inherited amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) and result in both loss of C9orf72 protein expression and production of potentially toxic RNA and dipeptide repeat proteins. In addition to ALS/FTD, C9orf72 repeat expansions have been reported in a broad array of neurodegenerative syndromes including Alzheimer’s disease. Here we show that C9orf72 deficiency promotes a change in the homeostatic signature in microglia and a transition to an inflammatory state characterized by an enhanced type I IFN signature. Furthermore, C9orf72-depleted microglia trigger age-dependent neuronal defects, in particular enhanced cortical synaptic pruning, leading to altered learning and memory behaviors in mice. Interestingly, C9orf72 deficient microglia promote enhanced synapse loss and neuronal deficits in a mouse model of amyloid accumulation, while paradoxically improving plaque clearance. These findings suggest that altered microglial function due to decreased C9orf72 expression directly contributes to neurodegeneration in repeat expansion carriers independent of gain of function toxicities.
Learning Objectives:
  • Understand the link between C9orf72 repeat expansions and neurodegenerative disorders
  • Explore the dual role of C9orf72-deficient microglia in amyloid accumulation
  • Examine the emerging technologies in C9orf72-ALS
Webinars will be available for unlimited on-demand viewing after live event.

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