Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive and selective loss of motor neurons. Causative genes for familial ALS (fALS), e.g. TARDBP or FUS/TLS, have been found, among which mutations within the profilin 1 (PFN1) gene have recently been identified in ALS18. To elucidate the mechanism whereby PFN1 mutations lead to neuronal death, we generated transgenic Drosophila melanogaster overexpressing human PFN1 in the retinal photoreceptor neurons. Overexpression of wild-type or fALS mutant PFN1 caused no degenerative phenotypes in the retina. Double overexpression of fALS mutant PFN1 and human TDP-43 markedly exacerbated the TDP-43-induced retinal degeneration, i.e. vacuolation and thinning of the retina, whereas co-expression of wild-type PFN1 did not aggravate the degenerative phenotype. Notably, co-expression of TDP-43 with fALS mutant PFN1 increased the cytoplasmic localization of TDP-43, the latter remaining in nuclei upon co-expression with wild-type PFN1, whereas co-expression of TDP-43 lacking the nuclear localization signal with the fALS mutant PFN1 did not aggravate the retinal degeneration. Knockdown of endogenous Drosophila PFN1 did not alter the degenerative phenotypes of the retina in flies overexpressing wild-type TDP-43 These data suggest that ALS-linked PFN1 mutations exacerbate TDP-43-induced neurodegeneration in a gain-of-function manner, possibly by shifting the localization of TDP-43 from nuclei to cytoplasm.
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PMID:Familial Amyotrophic Lateral Sclerosis-linked Mutations in Profilin 1 Exacerbate TDP-43-induced Degeneration in the Retina of Drosophila melanogaster through an Increase in the Cytoplasmic Localization of TDP-43. 2763 45

To detect the abnormal cortical thickness and disrupted brain resting-state functional connectivity (RSFC) in patients with systemic lupus erythematosus (SLE) without neuropsychiatric symptoms (non-NPSLE). Using T1-weighted 3D brain structural data, we first determined the regions with abnormal cortical thickness in a cohort of 33 adult female non-NPSLE patients. By taking brain regions with significantly reduced cortical thickness as the seeds, we calculated their RSFC based on the resting-fMRI data and detected the relationship between the RSFC and cortical thickness in the non-NPSLE patients. Compared to the controls, the non-NPSLE patients showed significantly cortical thinning in the left fusiform gyrus (FUS.L), left lingual gyrus (LING.L), right lingual gyrus (LING.R) and left superior frontal cortex (SFC.L). As for the RSFC, statistical analyses indicated that the abnormal cortical thickness in LING.L is associated with increased RSFC in the left posterior cingulate cortex (PCC.L), and cortical thinning in SFC.L associated with decreased RSFC in left cerebellum 6 (CRBL 6.L) in non-NPSLE patients. In addition, in non-NPSLE patients, the decreased cortical thickness in LING.L was correlated to the increased RSFC in PCC.L, and decreased cortical thickness in SFC.L was correlated to the decreased RSFC in CRBL 6.L. Our findings suggest that the cortical abnormalities may affect brain intrinsic connectivity in non-NPSLE patients.
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PMID:Cortical thickness reductions associate with abnormal resting-state functional connectivity in non-neuropsychiatric systemic lupus erythematosus. 2845 20