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Investigating the role of alpha-synuclein phosphorylation in the synucleinopathy olfactory system

Award Number: RF1NS146420
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: 06/25/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2029

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Investigating the role of alpha-synuclein phosphorylation in the synucleinopathy olfactory system - Project Summary The synucleinopathy disease process has been hypothesized to begin in the olfactory system (OS). Phosphorylated αsyn (PS129) may play a unique role in the synucleinopathy OS. The long-term goal of the proposed research is to understand the molecular factors responsible for αsyn aggregation in the OS. The objective of this proposal is to determine the role of PS129 in the synucleinopathy OS. The central hypothesis is that PS129 is involved in early synucleinopathy pathogenesis in the OS. Our rationale for the proposed studies is that determining PS129’s role in the synucleinopathy disease process will uncover novel therapeutic targets. The central hypothesis will be tested with three aims: 1) Determine the influence of PS129 on αsyn seeding, spread, and interactome throughout the OS 2) Differentiate physiological-PS129 and aggregated-PS129 interactomes in the OB 3) Determine the influence of PS129 on αsyn proteostasis in the OB. We will test these aims by applying our innovative techniques to several novel models of synucleinopathy and the human olfactory bulb to determine PS129’s role in the pathogenic process. The proposed research is significant because it will elucidate the fundamental factors of synucleinopathies to develop effective new treatments. The expected outcome of the proposed research is to provide a deeper understanding of molecular factors driving αsyn accumulation in brain structure where synucleinopathies are hypothesized to start (i.e., OB, OS).


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 = $1,212,318 )
2026	2026	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/30/2026	NEW	$1,212,318
														Subtotal = $1,212,318

Grand Total All Awards = $1,212,318

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Investigating the role of alpha-synuclein phosphorylation in the synucleinopathy olfactory system

Award Number: RF1NS146420

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: 06/25/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2029

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