Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autosomal dominant polycystic kidney disease (ADPKD) is a systemic disorder mainly involving the kidney. It affects one in 400-1000 live births. Early hypertension and progressive renal failure due to massive enlargement of cysts and fibrosis are hallmarks of the disease. ADPKD accounts for ~5-10% of cases requiring renal replacement therapy. But not only the kidneys are affected in ADPKD: cysts also occur in other organs such as the liver, pancreas, arachnoid membrane and seminal vesicles. Non-cystic manifestations of the diseases are intracranial aneurysms, hernias and valvular abnormalities. Complications in ADPKD usually result from kidney involvement and include cyst bleeding and cyst infection. However, serious extrarenal features such as subarachnoid haemorrhage can also occur. There is no specific treatment for ADPKD currently, but many molecules targeting up- or downregulated molecules in the renal epithelial cells are being tested. A clinical trial using tolvaptan (a vasopressin receptor antagonist) has demonstrated efficacy, while mTOR inhibitors have shown no positive effect in ADPKD. ACEIs and ARBs are the drugs of choice for treating hypertension in ADPKD. Until a specific therapy becomes available, early treatment of hypertension and lifestyle changes are encouraged.
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PMID:Autosomal dominant policystic kidney disease, more than a renal disease. 2473 82

Autosomal dominant polycystic kidney disease (ADPKD), the most frequent cause of genetic renal disease affecting approximately 4 to 7 million individuals worldwide and accounting for 7%-15% of patients on renal replacement therapy, is a systemic disorder mainly involving the kidney but cysts can also occur in other organs such as the liver, pancreas, arachnoid membrane and seminal vesicles. Though computed tomography and magnetic resonance imaging (MRI) were similar in evaluating 81% of cystic lesions of the kidney, MRI may depict septa, wall thickening or enhancement leading to upgrade in cyst classification that can affect management. A screening strategy for intracranial aneurysms would provide 1.0 additional year of life without neurological disability to a 20-year-old patient with ADPKD and reduce the financial impact on society of the disease. Current treatment strategies include reducing: cyclic adenosine monophosphate levels, cell proliferation and fluid secretion. Several randomised clinical trials (RCT) including mammalian target of rapamycin inhibitors, somatostatin analogues and a vasopressin V2 receptor antagonist have been performed to study the effect of diverse drugs on growth of renal and hepatic cysts, and on deterioration of renal function. Prophylactic native nephrectomy is indicated in patients with a history of cyst infection or recurrent haemorrhage or to those in whom space must be made to implant the graft. The absence of large RCT on various aspects of the disease and its treatment leaves considerable uncertainty and ambiguity in many aspects of ADPKD patient care as it relates to end stage renal disease (ESRD). The outlook of patients with ADPKD is improving and is in fact much better than that for patients in ESRD due to other causes. This review highlights the need for well-structured RCTs as a first step towards trying newer interventions so as to develop updated clinical management guidelines.
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PMID:Current management of autosomal dominant polycystic kidney disease. 2638 Jan 98

The mammalian target of rapamycin complex 1 (mTORC1) inhibitor rapamycin and its analogs are being increasingly used in solid-organ transplantation. A commonly reported side effect is male subfertility to infertility, yet the precise mechanisms of mTOR interference with male fertility remain obscure. With the use of a conditional mouse genetic approach we demonstrate that deficiency of mTORC1 in the epithelial derivatives of the Wolffian duct is sufficient to cause male infertility. Analysis of spermatozoa from Raptor fl/fl*KspCre mice revealed an overall decreased motility pattern. Both epididymis and seminal vesicles displayed extensive organ regression with increasing age. Histologic and ultrastructural analyses demonstrated increased amounts of destroyed and absorbed spermatozoa in different segments of the epididymis. Mechanistically, genetic and pharmacologic mTORC1 inhibition was associated with an impaired cellular metabolism and a disturbed protein secretion of epididymal epithelial cells. Collectively, our data highlight the role of mTORC1 to preserve the function of the epididymis, ductus deferens, and the seminal vesicles. We thus reveal unexpected new insights into the frequently observed mTORC1 inhibitor side effect of male infertility in transplant recipients.
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PMID:The Rapamycin-Sensitive Complex of Mammalian Target of Rapamycin Is Essential to Maintain Male Fertility. 2668 65