The understanding of the genetic basis of the Parkinson's disease (PD) and the correlation between genotype and phenotype has revolutionized our knowledge about the pathogenetic mechanisms of neurodegeneration, opening up exciting new therapeutic and neuroprotective perspectives. Genomic knowledge of PD is still in its early stages and can provide a good start for studies of the molecular mechanisms that underlie the gene expression variations and the epigenetic mechanisms that may contribute to the complex and characteristic phenotype of PD. In this study we used the software TRAM (Transcriptome Mapper) to analyse publicly available microarray data of a total of 151 PD patients and 130 healthy controls substantia nigra (SN) samples, to identify chromosomal segments and gene loci differential expression. In particular, we separately analyzed PD patients and controls data from post-mortem snap-frozen SN whole tissue and from laser microdissected midbrain dopamine (DA) neurons, to better characterize the specific DA neuronal expression profile associated with the late-stage Parkinson's condition. The default "Map" mode analysis resulted in 10 significantly over/under-expressed segments, mapping on 8 different chromosomes for SN whole tissue and in 4 segments mapping on 4 different chromosomes for DA neurons. In conclusion, TRAM software allowed us to confirm the deregulation of some genomic regions and loci involved in key molecular pathways related to neurodegeneration, as well as to provide new insights about genes and non-coding RNA transcripts not yet associated with the disease.
Contents In small animal practice, prostatic diseases are increasingly encountered. All dogs may experience prostatic disease, but particular care should be addressed to breeding dogs, in which prostatic affection may lead to decrease in semen quality and fertility. The most common prostatic disease is the benign prostatic hyperplasia (BPH) followed by prostatitis, prostatic neoplasia and prostate squamous metaplasia. These diseases do not have pathognomonic symptoms, therefore, making a correct diagnosis may not be easy. An accurate clinical examination and a correct diagnostic protocol are essential in order to begin the most appropriate treatment, and also to do a good prophylaxis where it is possible. BPH therapy is usually recommended when mild‐severe signs are present or if symptoms disturb the patient. New therapeutic approaches, both medical and surgical, allow to maintain fertility in most animals with prostatic disorders. Prostate cancer is relatively infrequent. Elective therapy is the surgical one, but it is considered palliative and can result in important post‐operative complications. The aim of this paper is to lay down the most appropriate diagnostic process describing the aetiologies of prostatic disease, their symptoms, the right investigative tools and therapy.
We have studied mitochondrial bioenergetics in HL180 cells (a cybrid line harboring the T14484C/ND6 and G14279A/ND6 mtDNA mutations of Leber hereditary optic neuropathy, leading to an ϳ50% decrease of ATP synthesis) and XTC.UC1 cells (derived from a thyroid oncocytoma bearing a disruptive frameshift mutation in MT-ND1, which impairs complex I assembly). The addition of rotenone to HL180 cells and of antimycin A to XTC.UC1 cells caused fast mitochondrial membrane depolarization that was prevented by treatment with cyclosporin A, intracellular Ca 2؉ chelators, and antioxidant. Both cell lines also displayed an anomalous response to oligomycin, with rapid onset of depolarization that was prevented by cyclosporin A and by overexpression of Bcl-2. These findings indicate that depolarization by respiratory chain inhibitors and oligomycin was due to opening of the mitochondrial permeability transition pore (PTP). A shift of the threshold voltage for PTP opening close to the resting potential may therefore be the underlying cause facilitating cell death in diseases affecting complex I activity. This study provides a unifying reading frame for previous observations on mitochondrial dysfunction, bioenergetic defects, and Ca 2؉ deregulation in mitochondrial diseases. Therapeutic strategies aimed at normalizing the PTP voltage threshold may be instrumental in ameliorating the course of complex I-dependent mitochondrial diseases.NADH:ubiquinone oxidoreductase (respiratory complex I; EC 1.6.5.3) is the first multiprotein complex of the oxidative phosphorylation system. Complex I contributes to the formation of the proton electrochemical gradient across the inner mitochondrial membrane by coupling proton translocation to electron transfer from NADH to ubiquinone. The proton gradient provides the driving force for ATP synthesis, ion transport, and maintenance of antioxidant defenses (1). Complex I is the largest respiratory chain complex with an estimated molecular mass of 900,000 Da; it is made up of seven subunits encoded by mtDNA (ND1-6 and ND4L) and 35 or more subunits encoded by nuclear genes (2, 3). Mutations in both the mitochondrial-encoded and the nuclearencoded human genes are known to cause complex I dysfunction, which is associated to a wide array of neurodegenerative diseases (3, 4) and to some types of tumor (5, 6). Pathogenic mutations have been identified in each of the seven NADH dehydrogenase (ND) 3 genes encoded by mtDNA. The clinical symptoms range from single organ or tissue diseases like Leber hereditary optic neuropathy (LHON) (7) to multisystemic disorders like mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) and Leigh syndrome (3, 4).It is established that mitochondrial dysfunction is strictly associated to activation of the intrinsic apoptotic pathway activated by the release of cytochrome c from mitochondria (8). In particular, complex I deficiency may sensitize cells to the action of death agonists that permeabilize the outer membrane, such as Bax, through mitocho...
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