Unlocking BIN1 function in oligodendrocytes and support of axon integrity
Ended Project Grant Awarded Last action
- Award ID
- R56AG083942
- Recipient
-
Texas A&M Agrilife Research UEI KU3DCFJJTVN3 Part of Texas A & M University System
- Awarding agency
-
National Institute on Aging
National Institutes of Health, Department of Health and Human Services
- Obligated
- $463,110
Award facts
- Assistance listing
- 93.866 Aging Research
- Completion date
- Originally
- Place of performance
- Texas, USA
Award details come from USAspending.gov.
Description
- Abstract
- Myelin is essential to rapid axonal impulse propagation and long-term integrity and survival of axons. Cerebral white matter alterations are common early features in late-onset alzheimer's disease (ad) brains, yet the cellular basis for these changes, long before the formation of senile plaques and TAU-containing neurofibrillary tangles, remains largely unexplored. Large unbiased transcriptome studies recently revealed alterations in myelination and axonal integrity at the early stage of alzheimer's disease, suggesting potential contributions of myelin-producing oligodendrocytes to ad pathogenesis. Interestingly, the second most prevalent genetic risk factor for late-onset alzheimer's disease, BIN1, is primarily expressed by mature oligodendrocytes. However, little is known about BIN1 functions in oligodendrocytes under physiological or pathophysiological conditions. Our preliminary data suggest that BIN1 protein is distributed at discrete locations in the cytoplasmic channels of uncompact myelin regions. Moreover, specific deletion of BIN1 in mature oligodendrocytes in adult brain results in age-dependent disruption of axon integrity and degeneration in the absence of overt demyelination. Because oligodendrocyte uses cytoplasmic channels to connect soma to distant peripheral processes that enwrap and interact with the axon, and because BIN1 plays a role in vesicle dynamics and membrane remodeling, we hypothesize that BIN1 functions in oligodendrocyte/axon communication and that loss or dysfunction of the oligodendrocyte-BIN1 axis aggravates age-associated myelin/axon decay and TAU pathology. In this research proposal, we will use oligodendrocyte-specific BIN1 conditional knockout mice and mutant mice carrying a late-onset the ad BIN1 variant to investigate the role of oligodendrocyte-BIN1 in myelin/axonal integrity in aging and in a tauopathy mouse model of ad. Understanding BIN1-associated physiological and pathophysiological pathways will likely provide new insights into how this risk factor might relate to the onset and/or progression of late-onset alzheimer's disease and related dementias.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | -$3,421 | |
| Original award | $466,531 |
Quick answers
Who received award R56AG083942?
R56AG083942 was awarded to Texas A&M Agrilife Research by National Institute on Aging (National Institutes of Health) on September 15, 2023.
How much is award R56AG083942 worth?
$463,110 has been obligated on R56AG083942.
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