Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0751651 (mitochondrial disease)
 1,844 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 22-year-old man with subacute necrotizing-encephalomyelopathy (SNE; Leigh's disease) was diagnosed as having progressive renal dysfunction. The clinical diagnosis of Leigh's disease was obtained by the typical central nervous lesions, abnormalities in other organs, and increased lactate concentrations in blood and cerebrospinal fluid. We performed an open biopsy of the right kidney. Light microscopic studies of the renal specimen showed diffuse glomerulocystic kidney (GCK) with tubulointerstitial damage. Electron microscopic examination showed marked swelling and increase in the number of mitochondria of the renal tubular epithelial cells. Therefore, it is suggested that mitochondrial disease seems to play an important role in developing GCK.
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PMID:Glomerulocystic kidney associated with subacute necrotizing-encephalomyelopathy. 1115

Leigh disease (LD) is one of the clinical phenotypes of mitochondrial OXPHOS disorders and also known as sub-acute necrotizing encephalomyelopathy. The disease has an incidence of 1 in 77,000 live births. Symptoms typically begin early in life and prognosis for LD patients is poor. Currently, no clinically effective treatments are available. Suitable animal and cellular models are necessary for the understanding of the neuropathology and the development of successful new therapeutic strategies. In this study we used the Ndufs4 knockout (Ndufs4(-/-)) mouse, a model of mitochondrial complex I deficiency. Ndusf4(-/-) mice exhibit progressive neurodegeneration, which closely resemble the human LD phenotype. When dissecting behavioral abnormalities in animal models it is of great importance to apply translational tools that are clinically relevant. To distinguish gait abnormalities in patients, simple walking tests can be assessed, but in animals this is not easy. This study is the first to demonstrate automated CatWalk gait analysis in the Ndufs4(-/-) mouse model. Marked differences were noted between Ndufs4(-/-) and control mice in dynamic, static, coordination and support parameters. Variation of walking speed was significantly increased in Ndufs4(-/-) mice, suggesting hampered and uncoordinated gait. Furthermore, decreased regularity index, increased base of support and changes in support were noted in the Ndufs4(-/-) mice. Here, we report the ability of the CatWalk system to sensitively assess gait abnormalities in Ndufs4(-/-) mice. This objective gait analysis can be of great value for intervention and drug efficacy studies in animal models for mitochondrial disease.
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PMID:Gait analysis in a mouse model resembling Leigh disease. 2636 24

The mitochondrial intramembrane rhomboid protease PARL has been implicated in diverse functions in vitro, but its physiological role in vivo remains unclear. Here we show that Parl ablation in mouse causes a necrotizing encephalomyelopathy similar to Leigh syndrome, a mitochondrial disease characterized by disrupted energy production. Mice with conditional PARL deficiency in the nervous system, but not in muscle, develop a similar phenotype as germline Parl KOs, demonstrating the vital role of PARL in neurological homeostasis. Genetic modification of two major PARL substrates, PINK1 and PGAM5, do not modify this severe neurological phenotype. Parl -/- brain mitochondria are affected by progressive ultrastructural changes and by defects in Complex III (CIII) activity, coenzyme Q (CoQ) biosynthesis, and mitochondrial calcium metabolism. PARL is necessary for the stable expression of TTC19, which is required for CIII activity, and of COQ4, which is essential in CoQ biosynthesis. Thus, PARL plays a previously overlooked constitutive role in the maintenance of the respiratory chain in the nervous system, and its deficiency causes progressive mitochondrial dysfunction and structural abnormalities leading to neuronal necrosis and Leigh-like syndrome.
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PMID:PARL deficiency in mouse causes Complex III defects, coenzyme Q depletion, and Leigh-like syndrome. 3057 22