Microglia- astrocyte crosstalk in cortical neurodegeneration of C9ORF72 ALS/FTD
Active Project Grant Awarded Last action
- Award ID
- F31NS139617
- Recipient
-
Dignity Health UEI SKX6AXF9ZTM3 Part of Commonspirit Health
- Awarding agency
-
National Institute of Neurological Disorders and Stroke
National Institutes of Health, Department of Health and Human Services
- Obligated
- $92,024
Award facts
- Assistance listing
- 93.853 Extramural Research Programs in the Neurosciences and Neurological Disorders
- Completion date 50% complete
- Place of performance
- Phoenix, AZ 85013, USA
Award details come from USAspending.gov.
Description
- Abstract
- Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by loss of spinal cord and cortical motor neurons, and frontotemporal dementia (FTD) is an early-onset dementia syndrome caused by the degeneration of the frontal and temporal lobes. The most common genetic cause of both these diseases is the ggggcc(G4C2) hexanucleotide repeat expansion (HRE) in the first intron of the C9ORF72. Much of the knowledge in C9ORF72-ALS/FTD disease pathogenesis thus far has come through investigations of neuronal disease mechanisms. Despite the large evidence of the active involvement of glial cells in neurodegeneration, little is known about the specific mechanisms. One question that remains unanswered is whether a glia-glia interaction is required to initiate neurodegeneration, or do astrocytes and microglia independently contribute to this process? We have shown an altered expression profile of microglia and astrocytes in the frontal cortex of C9ORF72 ALS/FTD patients. Additionally, in our ipsc modeling system we have seen aberrant expression of the NLRP3 inflammasome in microglia and astrocytes. These findings lead to the following hypothesis: microglia- astrocyte crosstalk underlies a chronic pro-inflammatory state in C9ORF72 ALS/FTD. To investigate this knowledge GAP, we will utilize state of the art human in vitro culture systems, which offer opportunities for easy cell-type specific manipulations and analyses while working with human patient-derived cells. We will utilize mono-culture systems to assess morphological, functional, RNA, and protein changes. We will validate our in vitro findings using ALS/FTD patient brain tissues on both the RNA and protein levels with the intent of understanding the cell-to-cell regulatory mechanisms of glia and their contribution to disease pathology. These studies will provide novel molecular targets and biomarkers of disease.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $46,300 | |
| Amendment | $0 | |
| Original award | $45,724 |
Quick answers
Who received award F31NS139617?
F31NS139617 was awarded to Dignity Health by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on August 13, 2025.
How much is award F31NS139617 worth?
$92,024 has been obligated on F31NS139617.
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