Nuclear inclusion

NI, nuclear inclusions (c), normal cytoplasmic localization (n), normal nuclear localization (membr), normal membrane localization. 

Duyckaerts C, Durr A, Cancel G, Brice A. Nuclear inclusions in spinocerebellar ataxia type 1. Acta Neuropathol Berl 1999 97 201-207. 

Renal Effects. The characteristics of early or acute lead-induced nephropathy in humans include nuclear inclusion bodies, mitochondrial changes, and cytomegaly of the proximal tubular epithelial cells dysfunction of the proximal tubules (Fanconi s syndrome) manifested as aminoaciduria, glucosuria, and phosphaturia with hypophosphatemia and increased sodium and decreased uric acid excretion. These effects appear to be reversible. Characteristics of chronic lead nephropathy include progressive interstitial fibrosis, dilation of tubules and atrophy or hyperplasia of the tubular epithelial cells, and few or no nuclear inclusion bodies, reduction in glomerular filtration rate, and azotemia. These effects are irreversible. The acute form is reported in lead-intoxicated children, whose primary exposure is via the oral route, and sometimes in lead workers. The chronic form is reported mainly in lead workers, whose primary exposure is via inhalation. Animal studies provide evidence of nephropathy similar to that which occurs in humans, particularly the acute form (see Section 2.2.3.2). 

Cummings CJ, Reinstein E, Sun Y, Antalffy B, Jiang Y, Ciechanover A, Orr HT, Beaudet AL, and Zoghbi HY (1999) Mutation of the E6-AP ubiquitin ligase reduces nuclear inclusion frequency while accelerating polyglutamine-induced pathology in SCAl mice. Neuron 24 879-892. 

GST, calmodulin-binding peptide, His-, FLAG-tag, protein A, glycoprotein D of HSV), or to enable its detection and/or selection, i.e. tags based on protein-reporters (/1-galactosidase, GFP, CAT, hGH) (Makrides, 1999). Tags can be fused to N- or C-terminal ends of the protein and a site for proteolytic cleavage is commonly included to eliminate the tag upon exploitation of its functionality. The proteases most commonly used are thrombin, enterokinase, factor Xa, and TEV (catalytic domain of Nia, the nuclear inclusion protein from tobacco etch virus). 

One might speculate that seeds arise from mutant forms of protein. For some of the discussed diseases this could be proven in cell culture models. Proteins like Huntingtin, amyloid-P and alpha-synuclein aggregate in vitro and in transfected COS cells. Models of SCA-3 show nuclear inclusions with wildtype and mutated protein [14]. Another example for this situation is found in AD plaques, where a peptide with a partial alpha-synuclein sequences seeds P-amyloid polymerization in vitro [32]. 

Clinically, lead nephropathy is seen as either reversible tubular dysfunction or as an irreversible interstitial nephropathy. Tubular toxicity occurs most commonly in children following acute exposure and is characterized by glucosuria, phosphaturia, aminoaciduria, and occasionally proteinuria. One unique morphological feature of lead exposure is the formation of nuclear inclusion bodies within renal tubular cells. These bodies are complexes between lead... 

The cellular mechanism of lead nephrotoxicity appears to be due to an alteration of calcium homeostasis. Lead (Pb ) competes with calcium (Ca " ") for transport, binding to calmodulin and at other cell calcium regulatory sites. Lead can accumulate in mitochondria using the calcium transporter and disrupt respiration. Interactions of lead with calmodulin can result in a disruption of the calcium messenger system to adversely affect normal cell function. The nuclear inclusion bodies may also alter the cellular function of DNA, although this interaction has not been fully elucidated. 

DNA-binding domain. This polyQ-expanded TBP, incapable of binding DNA, formed nuclear inclusions and caused a severe neurological phenotype in transgenic mice. Together, these results indicate that polyQ-expanded TBP is inhibitory to TATA-dependent transcription as it is unable to bind DNA productively [181,182]. PolyQ-expanded Htt exon 1 protein has also been shown to bind and sequester TBP [183]. In the case of mutant ataxin-7, HAT activity of the STAGA complex is compromised, and this has been directly linked to the retinal degeneration common in this disease [184, 185]. Transcriptional abnormalities have also been detected in ALS patients and mouse models thereof [186-188]. 

Singh G, Katyal SL, Torikata C. Carcinoma of type II pneumo-cytes PAS staining as a screening test for nuclear inclusions of surfactant-specific apoprotein. Cancer. 1982 50 946-948. 

Herpes simplex encephalitis Encephalitis (Table 20.2) Cowdry A amphophilic nuclear inclusions of 90-100 nm target capsids HSV Temporal or basilar frontal lobe(s) CNS frequently bilateral... 

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