Defining the role of SINE retrotransposons and inflammasome activation in Alzheimer's disease

Summary

This project investigates the role of SINE retrotransposons and inflammasome activation in the pathogenesis of Alzheimer's disease, aiming to define their functional roles, mechanisms, and explore therapeutic interventions.

What they want

The project tests the hypothesis that Alzheimer's disease pathology is exacerbated by NLRP3/NLRC4 activation induced by endogenous SINE RNA accumulation. Specific aims include: 1) Quantitating SINE RNA expression and inflammasome activation and mapping their cellular origins in the 5xFAD model of AD; 2) Determining the cellular mechanisms of SINE RNA-induced inflammasome activation in brain microglia, assessing its impact on Aβ phagocytosis, and evaluating if inflammasome inhibitors improve Aβ phagocytosis; and 3) Testing the effects of individual and dual inflammasome inhibitors on Aβ clearance, as well as cognitive and behavioral deficits in the 5xFAD model.

Deliverables

Quantitation of SINE RNA expression and inflammasome activation in the 5xFAD model of AD
Mapping of cellular origins of SINE RNAs and inflammasome activation in the 5xFAD model of AD
Determination of cellular mechanisms of SINE RNA-induced inflammasome activation in brain microglia
Assessment of SINE RNA's compromise on Aβ phagocytosis by microglia
Evaluation of inflammasome inhibitors' improvement on Aβ phagocytosis
Testing effects of inflammasome inhibitors on Aβ clearance in the 5xFAD model
Testing effects of inflammasome inhibitors on cognitive and behavioral deficits in the 5xFAD model
Deeper mechanistic understanding of the role of SINE RNAs-induced inflammasome activation in AD

Technical requirements

Investigation of Amyloid-β (Aβ) plaques and hyperphosphorylated Tau aggregates
Focus on NLRP3 and NLRC4 inflammasomes
Study of short interspersed elements (SINEs) and SINE RNAs
Investigation of DDX17 RNA helicase
Use of 5xFAD model of AD
Application of novel small molecule inhibitors of NLRC4-NLRP3 signaling
Techniques for quantitating SINE RNA expression
Methods for mapping cellular origins
Assays for inflammasome activation
Assays for Aβ phagocytosis

Market context

inferred from NAICS

Professional, Scientific & Technical Services

NAICS 541714

US market size: $2.0T
Typical award: $25K – $50M

Typical buyers

All federal civilianDoDStates

Commonly required

8(a)WOSBSDVOSBPE/PMP

Sector-level estimate — full code lookup not yet in catalog.