ANNOUNCEMENT

NOBEL PRIZE 2026

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NIHEUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENTR01

Homeostatic plasticity in mouse models of Jordan's Syndrome

Active
Institution
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, CA
Principal investigator
Graeme W Davis
Funding
$560K
Duration
2024–2029
Open portfolio

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Abstract

ABSTRACT Homeostatic plasticity (HP) encompasses a suite of compensatory physiological processes that stabilize neural function. It is widely hypothesized that homeostatic plasticity will be linked to the cause and/or severity of neurodevelopmental disorders including autism and intellectual disability. Yet, there remains limited molecular, mechanistic information to directly connect homeostatic plasticity to neurological and neurodevelopmental disorders. We recently demonstrated that the homeostatic regulation of presynaptic neurotransmitter release is expressed in adult mammalian brain. We present new data demonstrating that presynaptic homeostatic plasticity is blocked in a novel mouse model of severe intellectual disability, termed Jordan’s syndrome in human. We will build upon new genetic and biochemical evidence and establish a mechanistic framework to directly associate homeostatic plasticity with the genetic underpinnings of Jordan’s syndrome. These data greatly expand our mechanistic and phenotypic understanding of Jordan’s syndrome and open the door to future therapeutic approaches to ameliorate the pathophysiological severity of Jordan’s syndrome. Ultimately, this research has broad implications for the treatment of neurodevelopmental disorders based upon the rational manipulation of homeostatic signaling.

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R01EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENTNeurodifferentiation, Plasticity, Regeneration and Rhythmicity Study Section[NDPR]presynapticneurodevelopmentalplasticityhomeostaticsyndromeneurodevelopmental disordersdisabilityintellectual disability

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