Therapeutic targeting of proteostasis in Fragile X Syndrome
About This Grant
Project Summary/Abstract: Project Abstract: Neurodevelopmental disorders are increasingly prevalent, and no mechanism-based therapeutics are available. Discovering the cellular and molecular alterations that are driving synaptic and circuit disruptions in these disorders is essential for developing targeted treatment strategies. In previous work, we and others identified an accelerated rate of protein synthesis in neurons of the Fmr1-/y mouse model of Fragile X Syndrome (FXS), the most commonly identified monogenic cause of intellectual disability. In more recent work, we now show that protein degradation by the ubiquitin proteasome system (UPS) is similarly elevated in Fmr1- /y neurons. Furthermore, inhibiting this pathway lowers neuronal hyperactivation and seizures in the Fmr1-/y mouse. This suggests the constitutive elevation of proteasome activity in Fmr1-/y neurons is detrimental. In this proposal we will: (1) Interrogate the mechanism driving increased UPS activity in Fmr1-/y brain. Specifically, we will test the hypothesis that increased proteasome activity in Fmr1-/y neurons is driven by excessive translation of aberrant proteins. (2) Determine the link between accelerated protein degradation and increased excitability. Specifically, we will test the hypothesis that excessive misfolding and degradation of GABA-ARs contributes to hyperexcitability in Fmr1-/y neurons. (3) Investigate UPS inhibition as a novel therapeutic strategy for FXS. Specifically, we will test the hypothesis that proteasome inhibition can resolve multiple hippocampal and cortical plasticity phenotypes in the Fmr1-/y mouse.
Grant Summary
Therapeutic targeting of proteostasis in Fragile X Syndrome is a NIMH - National Institute of Mental Health grant providing up to $497K for university, nonprofit, healthcare org. Applications are due 2031-04-30 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $497K
2031-04-30
- 1Confirm your organization is eligible for Therapeutic targeting of proteostasis in Fragile X Syndrome from NIMH - National Institute of Mental Health, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIMH - National Institute of Mental Health before the deadline.
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Therapeutic targeting of proteostasis in Fragile X Syndrome: Frequently Asked Questions
Who is eligible for the Therapeutic targeting of proteostasis in Fragile X Syndrome?
Therapeutic targeting of proteostasis in Fragile X Syndrome is offered by NIMH - National Institute of Mental Health and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Therapeutic targeting of proteostasis in Fragile X Syndrome provide?
Therapeutic targeting of proteostasis in Fragile X Syndrome provides up to $497K per award from NIMH - National Institute of Mental Health. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Therapeutic targeting of proteostasis in Fragile X Syndrome deadline?
Applications for Therapeutic targeting of proteostasis in Fragile X Syndrome are due 2031-04-30 (open). Because deadlines can change, verify the date with the funder, NIMH - National Institute of Mental Health, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Therapeutic targeting of proteostasis in Fragile X Syndrome?
To apply for Therapeutic targeting of proteostasis in Fragile X Syndrome, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIMH - National Institute of Mental Health.