Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Identifying mechanisms of axon length-dependent degeneration

Award Number: R01NS143223
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/21/2026
PERIOD OF PERFORMANCE END DATE: 12/31/2030

Group Awards By:

View Award Description

Identifying mechanisms of axon length-dependent degeneration - PROJECT SUMMARY Many neurodegenerative disorders (NDDs) preferentially affect neurons with long or complex axonal arbors. However, our understanding of this specific vulnerability is limited. Using Drosophila melanogaster as a model system, we identified a genetic pathway regulating neuronal production of the proinflammatory cytokine upd3, an Interleukin-6 orthologue, which drives axon length-dependent presynapse removal by glial cells. Remarkably, ectopic upd3 expression induces axon length- dependent presynapse loss in wild-type neurons, demonstrating that long axons and their connections are intrinsically vulnerable to removal. Our central hypothesis, based on extensive preliminary data analyzing axon length-dependent synaptic phenotypes at the structural, functional and behavioral level is that axon length-dependent degeneration is driven by neuronal stress-induced inflammatory cytokine production and subsequent activation of microglia-like phagocytes that recognize signals produced in a length-dependent fashion on target axons. We rigorously test this hypothesis, defining the features of the upd3 signaling system, identifying and characterizing the phagocytic glia, and defining intrinsic signals underlying the vulnerability of long axons to degeneration. Altogether, our studies will provide fundamental insight into a mechanisms of axon length-dependency in degeneration, addressing a fundamental gap in our understanding of NDDs.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $502,070 )
2026	2026	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/21/2026	NEW	$502,070
														Subtotal = $502,070

Grand Total All Awards = $502,070

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Identifying mechanisms of axon length-dependent degeneration

Award Number: R01NS143223

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/21/2026

PERIOD OF PERFORMANCE END DATE: 12/31/2030

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer