Pflügers Archiv - European Journal of Physiology

, Volume 455, Issue 5, pp 787–797 | Cite as

Rho-linked genes and neurological disorders

  • Nael Nadif Kasri
  • Linda Van AelstEmail author
Invited Review


Mental retardation (MR) is a common cause of intellectual disability and affects approximately 2 to 3% of children and young adults. Many forms of MR are associated with abnormalities in dendritic structure and/or dendritic spine morphology. Given that dendritic spine morphology has been tightly linked to synaptic activity, altered spine morphology has been suggested to underlie or contribute to the cognitive disabilities associated with MR. The structure and dynamics of dendritic spines is determined by its underlying actin cytoskeleton. Signaling molecules and cascades important for cytoskeletal regulation have therefore attracted a great deal of attention. As key regulators of both the actin and microtubule cytoskeletons, it is not surprising that the Rho GTPases have emerged as important regulators of dendrite and spine structural plasticity. Significantly, mutations in regulators and effectors of Rho GTPases have been associated with diseases affecting the nervous system, including MR and amyotropic lateral sclerosis (ALS). Here, we will discuss Rho GTPase-related genes and their signaling pathways involved in MR and ALS.


Mental retardation Dendritic spines Actin cytoskeleton Rho GTPases X-linked mental retardation Amyotrophic lateral sclerosis 



Alzheimer disease


amyotropic lateral sclerosis


α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor


Rho guanine–nucleotide exchange factor 6


actin-related proteins 2 and 3

amyloid β


cAMP-responsive element-binding protein


cytoplasmic FMR1 interacting protein


fragile-X mental retardation protein


fragile-X mental retardation-1 gene


fragile-X syndrome


GTPase activating proteins


guanine–nucleotide dissociation inhibitor


guanine–nucleotide exchange factor


Lin-11, Isl-1, and Mec-3 kinase


long-term depression


long-term potentiation


mental disorder-associated GAP protein


metabotropic glutamate receptor


myosin light chain


myosin light chain kinase


myosin light chain phosphatase


mental retardation


non-syndromic X-linked mental retardation


syndromic X-linked mental retardation




p21-activated kinases




Wiskott–Aldrich syndrome protein


WASP family Verprolin-homologous protein


Williams–Beuren syndrome


X-linked mental retardation



L.V.A is supported by the National Institutes of Health, National Science Foundation, and National Alliance for Autism Research. N.N.K is a postdoctoral fellow from the Fund for Scientific Research Flanders and is supported by the Human Frontiers Science Program.


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© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Cold Spring Harbor LaboratoryCold Spring HarborUSA

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