COX AND MITOCHONDRIAL F1F0-ATPASE (ATP SYNTHASE) ACTIVITIES IN PLATELETS AND BRAIN FROM PATIENTS WITH ALZHEIMER'S DISEASE

Evidence suggests that mitochondrial dysfunction is prominent in Alzheimer's disease (AD). A failure of one or more of the mitochondrial electron transport chain enzymes or of F(1)F(0)-ATPase (ATP synthase) could compromise brain energy stores, generate damaging reactive oxygen species (ROS), and lead to neuronal death. In the present study, cytochrome c oxidase (COX) and F(1)F(0)-ATPase activities of isolated mitochondria from platelets and postmortem motor cortex and hippocampus from AD patients and age-matched control subjects were assayed. Compared with controls, COX activity was decreased significantly in platelets (-30%, P < 0.01, n = 20) and hippocampus (-35 to -40%, P < 0.05, n = 6), but not in motor cortex from the AD patients. In contrast, in AD platelets and brain tissues, F(1)F(0)-ATP hydrolysis activity was not significantly changed. Moreover, the ATP synthesis rate was similar in mitochondria of platelets from AD patients and controls. These results demonstrate that COX but not F(1)F(0)-ATPase is a mitochondrial target in AD, in both a brain association area and in platelets. A reduced COX activity may make the tissue vulnerable to excitotoxicity or reduced oxygen availability

Pebble industry of Rimini area

Sono descritte le industrie del Paleolitico inferiore dell'area rimines

Concorso Internazionale per il “Welcome Center” delle Grotte di Frasassi, Genga, 2° Premio

La gola di Frasassi è scavata nei calcari grigi e compatti strapiombanti sul fiume Sentino che si snoda, prima di confluire nel fiume Esino, tra le pendici contrapposte dei monti Ginguno e Vallemontagnana. All’interno di questa gola è presente una vegetazione boschiva che spunta rigogliosa tra i declivi, condizionata dall’esposizione, dall’altitudine e dal terreno. In questo luogo era necessario porre in essere il recupero edilizio e ambientale dell’area a servizio delle meravigliose grotte scoperte nel 1970 casualmente da un gruppo di alpinisti del Club Alpino Italiano di Ancona. Su di essa insistono trentaquattro botteghe di venditori ambulanti che, attraverso questo concorso di idee, aspirano a ottenere una sede in una stuttura stabile. L’obiettivo di progetto era quello di abbinare alla magia della visita alle grotte la piacevolezza di una sosta passata a scegliere un ricordo nel bosco dei regali, una piazza alberata immersa in un parco naturale ricco di suggestioni e luoghi d’incontro, così da trasformare l’attesa della visita spereologica in un’occasione per scoprire la bellezza austera del paesaggio circostante. Le attività commerciali vengono disposte lungo il perimetro della nuova piazza ellittica così da formare un edificio porticato su ambo i lati, da realizzarsi in pietra e legno con una copertura a due falde rivestita in rame preossidato. Una piccola scarpata raccorda la quota di campagna con un muretto in pietra che delimita il porticato esterno, in modo da ottenere la riduzione dell’altezza dell’edificio e un percorso in trincea per l’approvigionamento delle attività commerciali. Nel centro della piazza viene collocata una tenso-struttura che ospita la biglietteria, l’ufficio informazioni e un piccolo spazio espositivo. Il parco costituisce uno degli elementi portanti dell’intero progetto connettendo e integrando il nuovo sistema edificato. Il progetto ha vinto il secondo premio

Biochemical-clinical correlation in patients with different loads of the mitochondrial DNA T8993G mutation

Objective: To investigate the correlation between biochemical and clinical phenotype in 6 patients from 3 unrelated families with different mutation loads (heteroplasmy) of the T8993G mitochondrial DNA mutation associated with neuropathy, ataxia, and retinitis pigmentosa-Leigh syndrome. Methods: We studied adenosine triphosphate (ATP) synthase activity (synthesis and hydrolysis) in platelet-derived submitochondrial particles and assessed mutant loads both in platelets used for biochemical analysis and in other available tissues. Biochemical and molecular results were correlated with clinical features. Results: The rate of ATP hydrolysis was normal, but ATP synthesis was severely impaired (30% to 4% of residual activity) in patients harboring 34% to 90% mutant mitochondrial DNA, without any evidence of a threshold for the expression of this defect. There was little variation in heteroplasmy among tissues from each patient, but wider variability was detected in 2 mothers. Correlation of heteroplasmy and clinical and biochemical features suggested that ATP synthesis is defective at mutant loads as low as 34% and is extremely reduced at mutant loads above 80% when the phenotype is neuropathy, ataxia, and retinitis pigmentosa-Leigh syndrome. Conclusions: This study indicates a close relationship between tissue heteroplasmy, expression of the biochemical defect in platelets, and clinical involvement. The biochemical defect was greater than previously reported, and we found no evidence of a biochemical threshold. The uniform distribution of high mutant loads among our patients' tissues suggests a differential tissue-specific reliance on mitochondrial ATP synthesis

Biochemical-clinical correlation in patients with different loads of the mitochondrial DNA T8993G mutation

none11Objective: To investigate the correlation between biochemical and clinical phenotype in 6 patients from 3 unrelated families with different mutation loads (heteroplasmy) of the T8993G mitochondrial DNA mutation associated with neuropathy, ataxia, and retinitis pigmentosa-Leigh syndrome. Methods: We studied adenosine triphosphate (ATP) synthase activity (synthesis and hydrolysis) in platelet-derived submitochondrial particles and assessed mutant loads both in platelets used for biochemical analysis and in other available tissues. Biochemical and molecular results were correlated with clinical features. Results: The rate of ATP hydrolysis was normal, but ATP synthesis was severely impaired (30% to 4% of residual activity) in patients harboring 34% to 90% mutant mitochondrial DNA, without any evidence of a threshold for the expression of this defect. There was little variation in heteroplasmy among tissues from each patient, but wider variability was detected in 2 mothers. Correlation of heteroplasmy and clinical and biochemical features suggested that ATP synthesis is defective at mutant loads as low as 34% and is extremely reduced at mutant loads above 80% when the phenotype is neuropathy, ataxia, and retinitis pigmentosa-Leigh syndrome. Conclusions: This study indicates a close relationship between tissue heteroplasmy, expression of the biochemical defect in platelets, and clinical involvement. The biochemical defect was greater than previously reported, and we found no evidence of a biochemical threshold. The uniform distribution of high mutant loads among our patients' tissues suggests a differential tissue-specific reliance on mitochondrial ATP synthesis.noneCarelli V.; Baracca A.; Barogi S.; Pallotti F.; Valentino M.L.; Montagna P.; Zeviani M.; Pini A.; Lenaz G.; Baruzzi A.; Solaini G.Carelli, V.; Baracca, A.; Barogi, S.; Pallotti, F.; Valentino, M. L.; Montagna, P.; Zeviani, M.; Pini, A.; Lenaz, G.; Baruzzi, A.; Solaini, G