Role of Excessive Protein Synthesis in the Ontogeny of FXS
Excessive neuronal protein synthesis is not just a symptom but appears to cause early synaptic wiring defects in Fragile X — highlighting translation control as a key target.
Altered Dendritic Synthesis of Postsynaptic Scaffold Protein Shank1 in Fragile X Syndrome
Loss of FMRP leads to excess synthesis of the scaffold protein Shank1 at dendrites. Elevated Shank1 may impair synaptic pruning and drive Fragile X spine pathology.
The Slack Potassium Ion channel is a Therapeutic Target for Fragile X
With $282,000 in funding from FRAXA Research Foundation, Dr. Leonard Kaczmarek and colleagues explored association of Slack channels with the Fragile X protein (FMRP).
Composition and Localization of Dendritic mRNAs in Fragile X Syndrome
With a $80,000 grant from FRAXA Research Foundation over 2 years, Drs. Smith and Wang are investigating which proteins, as well as the mRNA’s that code those proteins, are dysregulated in Fragile X. They have developed a elegant system to visualize the proteins and mRNA’s and determine where they are spacially in the neuron. This will help to better understand the root causes of Fragile X syndrome and to design targeted treatments.
Basic Mechanisms of Disease and Potential Therapeutic Strategies
Dr. Stephen Warren’s FRAXA-funded research at Emory led to the Fragile X gene discovery and new breakthroughs using stem cells and model systems.
Role of FMRP in the Regulation of Synaptic Plasticity
FRAXA’s $1M support helped Drs. Greenough and Weiler reveal FMRP’s role at synapses, shaping today’s understanding of Fragile X syndrome.
Using Fenobam to Reduce APP and Abeta in Fragile X Mice
With a $130,000 grant from FRAXA Research Foundation over 2008-2009, Drs. James Malter and Cara Westmark at the University of Wisconsin studied the relationship between the Fragile X protein FMRP and APP, a protein important to the pathology of Alzheimer’s Disease. APP may also contribute to the pathology of Fragile X, and its major metabolite, Aß, may contribute to abnormal protein synthesis via a positive feedback loop. This project sought to restore normal dendritic protein synthesis in Fragile X mice by breaking into this loop.
FMRP-MAP1b RNA Interactions in Fragile X Syndrome
With a $95,000 grant from FRAXA Research Foundation from 2006-2007, Dr. Mihaela Mihailescu and her team at Dusquesne University studied the relationship between FMRP, RNA sequences, and G quartet structure. Results published.
Electrophysiological, Biochemical and Immunohistochemical Characterization of Kv3.1 in Auditory Brainstem Nuclei in the Fragile X Knockout Mouse
Dr. Leonard Kaczmarek’s Yale lab revealed how Fragile X disrupts potassium channels, impairing auditory processing and fueling sensory overload.
Defining Functional Domains of FMRP and Uncovering its Partners via Large Scale Mutagenesis in Drosophila
With $80K from FRAXA, Dr. Yong Zhang at the Chinese Academy of Sciences identified genes that suppress Fragile X and explored FMRP function.
Splicing Variations of the Fragile X Gene
An $80K FRAXA grant helped Dr. David Morris at the University of Washington explore FMRP isoform variation and brain expression.
Drosophila CYFIP, a Molecular Link Between Actin Cytoskeleton Remodeling and Fragile X
With $130K from FRAXA, Dr. Angela Giangrande at Université Louis Pasteur studied dendrite, mRNA, and cytoskeleton interactions in fruit flies.
Genetic and Behavioral Analyses of the dFMR1 Pathway in Drosophila Peripheral Nervous System
FRAXA’s $160K grant supported Dr. Fen-Biao Gao’s UC team in exploring the connection between mRNA and FMRP.
Composition and Dynamics of FMRP-Containing RNP Complexes
A $30K FRAXA grant helped Dr. Barbara Bardoni at INSERM, France, explore the biochemistry and function of the Fragile X protein.
Role of MicroRNAs in Fragile X Syndrome
A $70K FRAXA grant helped Drs. Thomas Tuschl and Neil Renwick study FMRP–miRNA links to identify better treatment targets for Fragile X.
Transport, Anchoring and Translation of FMRP-Associated mRNAs
FRAXA’s $40K grant supported Dr. Vladimir Gelfand’s Northwestern team in exploring links between mGluR, mRNA, and FMRP.
FMRP Function in the Xenopus Visual System
With $75K from FRAXA, Dr. Holly Cline at Cold Spring Harbor studied Fragile X proteins and mRNA regulation in tadpoles.
Fruit Fly Helps Reveal the Secrets of Fragile X
FRAXA’s $50K grant supported Dr. Bassem Hassan’s Flanders team in using fruit flies to model Fragile X and guide future therapy studies.
DFXR and Synaptic Tagging in Drosophila (Fruit Flies)
FRAXA’s $135K grant supported Dr. Jerry Yin’s Fragile X fruit fly studies on memory formation at Wisconsin’s Waisman Center.
Understanding the Function of Fragile X Protein in Drosophila
FRAXA-funded Tokushima researchers mapped the Drosophila FMR1 gene and its pathways, revealing how Fragile X disrupts cell function.
Isolating and Characterizing the mRNAs That Bind FMRP
With $60K from FRAXA, Dr. Denman’s team investigated how the Fragile X protein FMRP functions in the brain.
Structure of FMRP
With $68K from FRAXA, Dr. Lynne Regan at Yale studied how protein shapes influence Fragile X function. Results were published.
Identification of Specific RNA Targets of FMRP
FRAXA-funded Dr. Darnell’s Rockefeller team uncovered how FMRP works and how its absence alters brain function. Published results.
Molecular Interactions Between FMRP and Protein Translation Apparatus
FRAXA-funded Dr. Bagni uncovered how Fragile X disrupts protein synthesis control, advancing molecular understanding. Published results.