Mitochondrial Dysfunction Combined with High Calcium Load Leads to Impaired Antioxidant Defense Underlying the Selective Loss of Nigral Dopaminergic Neurons.

Mitochondrial dysfunction is critically involved in Parkinson's disease, characterized by loss of dopaminergic neurons (DaNs) in the substantia nigra (SNc), whereas DaNs in the neighboring ventral tegmental area (VTA) are much less affected. In contrast to VTA, SNc DaNs engage calcium channels to generate action potentials, which lead to oxidant stress by yet unknown pathways. To determine the molecular mechanisms linking calcium load with selective cell death in the presence of mitochondrial deficiency, we analyzed the mitochondrial redox state and the mitochondrial membrane potential in mice of both sexes with genetically induced, severe mitochondrial dysfunction in DaNs (MitoPark mice), at the same time expressing a redox-sensitive GFP targeted to the mitochondrial matrix.

DARS2 protects against neuroinflammation and apoptotic neuronal loss, but is dispensable for myelin producing cells.

Although mitochondria are ubiquitous, each mitochondrial disease has surprisingly distinctly different pattern of tissue and organ involvement. Congruently, mutations in genes encoding for different mitochondrial tRNA synthetases result in the development of a very flamboyant group of diseases. Mutations in some of these genes, including aspartyl-tRNA synthetase (DARS2), lead to the onset of a white matter disease-leukoencephalopathy with brainstem and spinal cord involvement, and lactate elevation (LBSL) characterized by progressive spastic ataxia and characteristic leukoencephalopathy signature with multiple long-tract involvements.

Prothrombin 3'end gene variants in isolated pulmonary embolism--the first report of FIIc.*64_*66del and FIIc.*303T>C variants.

Objective: Pulmonary embolism is usually considered as a complication of deep vein thrombosis, but there are still a number of cases of isolated pulmonary embolism. We aimed to investigate whether prothrombin 3'end gene variants might play a significant role in the pathogenesis of isolated pulmonary embolism.

Methods And Results: In this study 100 patients with isolated pulmonary embolism and 100 controls were screened by DNA sequencing.

The 3' end prothrombin gene variants in serbian patients with idiopathic thrombophilia.

Thrombophilia is a multifactorial disorder that arises from the interaction of acquired and genetic risk factors. Despite the significant efforts made to understand the etiology of this disease, there are still a certain number of patients suffering from idiopathic thrombophilia. The aim of this study was to screen the 3' end of the prothrombin (FII) gene, which is susceptible to gain-of-function mutations due to its non canonical architecture, in patients with idiopathic thrombophilia and to determine its eventual role in the pathogenesis of thrombophilia.