Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a 10-year-old Down syndrome patient who developed dystonia, choreoathetosis, dysarthria, and dysphagia beginning with hemiparesis. Cranial computed tomography disclosed bilateral calcification in the globus pallidus which resembled a sign of premature aging. Conversely, the clinical course and magnetic resonance imaging findings resembled those of Hallervorden-Spatz syndrome.
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PMID:Globus pallidus calcification in Down syndrome with progressive neurologic deficits. 153 15

Morphological abnormalities of the bounding membranes of the nucleus have long been associated with human diseases from cancer to premature aging to neurodegeneration. Studies over the past few decades support that there are both cell intrinsic and extrinsic factors (e.g. mechanical force) that can lead to nuclear envelope 'herniations', a broad catch-all term that reveals little about the underlying molecular mechanisms that contribute to these morphological defects. While there are many genetic perturbations that could ultimately change nuclear shape, here, we focus on a subset of nuclear envelope herniations that likely arise as a consequence of disrupting physiological nuclear membrane remodeling pathways required to maintain nuclear envelope homeostasis. For example, stalling of the interphase nuclear pore complex (NPC) biogenesis pathway and/or triggering of NPC quality control mechanisms can lead to herniations in budding yeast, which are remarkably similar to those observed in human disease models of early-onset dystonia. By also examining the provenance of nuclear envelope herniations associated with emerging nuclear autophagy and nuclear egress pathways, we will provide a framework to help understand the molecular pathways that contribute to nuclear deformation.
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PMID:Fantastic nuclear envelope herniations and where to find them. 3002 68

The function of the nucleus depends on the integrity of the nuclear lamina, an intermediate filament network associated with the linker of nucleoskeleton and cytoskeleton (LINC) complex. The LINC complex spans the nuclear envelope and mediates nuclear mechanotransduction, the process by which mechanical signals and forces are transmitted across the nuclear envelope. In turn, the AAA+ ATPase torsinA is thought to regulate force transmission from the cytoskeleton to the nucleus. In humans, mutations affecting nuclear envelope-associated proteins cause laminopathies, including progeria, myopathy, and dystonia, though the extent to which endogenous mechanical stresses contribute to these pathologies is unclear. Here, we use the Caenorhabditis elegans germline as a model to investigate mechanisms that maintain nuclear integrity as germ cell nuclei progress through meiotic development and migrate for gametogenesis-processes that require LINC complex function. We report that decreasing the function of the C. elegans torsinA homolog, OOC-5, rescues the sterility and premature aging caused by a null mutation in the single worm lamin homolog. We show that decreasing OOC-5/torsinA activity prevents nuclear collapse in lamin mutants by disrupting the function of the LINC complex. At a mechanistic level, OOC-5/torsinA promotes the assembly or maintenance of the lamin-associated LINC complex and this activity is also important for interphase nuclear pore complex insertion into growing germline nuclei. These results demonstrate that LINC complex-transmitted forces damage nuclei with a compromised nuclear lamina. Thus, the torsinA-LINC complex nexus might comprise a therapeutic target for certain laminopathies by preventing damage from endogenous cellular forces.
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PMID:Decreased mechanotransduction prevents nuclear collapse in a Caenorhabditis elegans laminopathy. 3322 89