Repository logo

Browsing by Author "Grazina, M"

Now showing 1 - 6 of 6
  • Frontotemporal dementia and mitochondrial DNA transitions
    Publication . Grazina, M; Silva, F; Santana, I; Santiago, B; Mendes, C; Simões, M; Oliveira, M; Cunha, L; Oliveira, CR
    Frontotemporal dementia (FTD) is the second most common type of primary degenerative dementia. Some patients present an overlap between Alzheimer's disease (AD) and FTD both in neuropathological and clinical aspects. This may suggest a similar overlap in physiopathology, namely an involvement of mitochondrial DNA (mtDNA) in FTD, as it has been associated to AD. To determine if mtDNA is involved in FTD, we performed a Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analysis, specific to mtDNA NADH Dehydrogenase subunit 1 (ND1) nucleotides 3337-3340, searching for mutations previously described in Parkinson's and AD patients. We could identify one FTD patient with two mtDNA transitions: one already known (3316 G-to-A) and another unreported (3337 G-to-A). Additionally, mitochondrial respiratory chain complex I activity was reduced in leukocytes of this patient (36% of the control mean activity). To our knowledge, this is the first report of mtDNA variants in FTD patients.
    2004Journal article Open access Show more
  • Genetic basis of Alzheimer's dementia: role of mtDNA mutations
    Publication . Grazina, M; Pratas, J; Silva, F; Oliveira, S; Santana, I; Oliveira, CR
    Alzheimer's disease (AD) is the most common neurodegenerative disorder associated to dementia in late adulthood. Amyloid precursor protein, presenilin 1 and presenilin 2 genes have been identified as causative genes for familial AD, whereas apolipoprotein E epsilon4 allele has been associated to the risk for late onset AD. However, mutations on these genes do not explain the majority of cases. Mitochondrial respiratory chain (MRC) impairment has been detected in brain, muscle, fibroblasts and platelets of Alzheimer's patients, indicating a possible involvement of mitochondrial DNA (mtDNA) in the aetiology of the disease. Several reports have identified mtDNA mutations in Alzheimer's patients, suggesting the existence of related causal factors probably of mtDNA origin, thus pointing to the involvement of mtDNA in the risk contributing to dementia, but there is no consensual opinion in finding the cause for impairment. However, mtDNA mutations might modify age of onset, contributing to the neurodegenerative process, probably due to an impairment of MRC and/or translation mechanisms.
    2006Journal article Open access Show more
  • Identification of a novel deletion in SURF1 gene: Heterogeneity in Leigh syndrome with COX deficiency
    Publication . Ribeiro, C; Macário, MC; Viegas, AT; Pratas, J; Santos, MJ; Simões, M; Mendes, C; Bacalhau, M; Garcia, P; Diogo, L; Grazina, M
    Leigh syndrome (LS) is a rare, progressive neurodegenerative mitochondrial disorder of infancy. It is a genetically heterogeneous disease. The mutations in SURF1 gene are the most frequently known cause. Here two cases of LS likely caused by SURF1 gene variants are reported: a 39-year-old male patient with a novel homozygous deletion (c.-11_13del), and a case of a 6-year-old boy with the same deletion and a nonsense mutation (c.868dupT), both in heterozygosity. Blue native PAGE showed absence of assembled complex IV. This is the first report of a variant that may abolish the SURF1 gene initiation codon in two LS patients.
    2016-11Journal article Open access Show more
  • Mitochondrial DNA Variants in a Portuguese Population of Patients with Alzheimer’s Disease
    Publication . Grazina, M; Silva, F; Santana, I; Pratas, J; Santiago, B; Oliveira, M; Carreira, I; Cunha, L; Oliveira, CR
    Alzheimer's disease (AD) is the most common neurodegenerative disorder associated with dementia in late adulthood. Mitochondrial respiratory chain impairment has been detected in the brain, muscle, fibroblasts and platelets of AD patients, indicating a possible involvement of mitochondrial DNA (mtDNA) in the etiology of the disease. Several reports have identified mtDNA mutations in AD patients, but there is no consensual opinion regarding the cause of the impairment. We have studied mtDNA NADH dehydrogenase subunit 1 nucleotides 3337-3340, searching for mutations. Our study group included 129 AD patients and 125 healthy age-matched controls. We have found alterations in two AD patients: one had two already known mtDNA modifications (3197 T-C and 3338 T-C) and the other a novel transition (3199 T-C) which, to our knowledge, has not been described before.
    2005Journal article Open access Show more
  • Mitochondrial-dependent apoptosis in Huntington's disease human cybrids
    Publication . Ferreira, IL; Nascimento, MV; Ribeiro, MH; Almeida, S; Cardoso, SM; Grazina, M; Pratas, J; Santos, MJ; Januário, C; Oliveira, CR; Rego, AC
    We investigated the involvement of mitochondrial-dependent apoptosis in Huntington's disease (HD) vs. control (CTR) cybrids, obtained from the fusion of human platelets with mitochondrial DNA-depleted NT2 cells, and further exposed to 3-nitropropionic acid (3-NP) or staurosporine (STS). Untreated HD cybrids did not exhibit significant modifications in the activity of mitochondrial respiratory chain complexes I-IV or in mtDNA sequence variations suggestive of a primary role in mitochondrial susceptibility in the subpopulation of HD carriers studied. However, a slight decrease in mitochondrial membrane potential and increased formation of intracellular hydroperoxides was observed in HD cybrids under basal conditions. Furthermore, apoptotic nuclei morphology and a moderate increase in caspase-3 activation, as well as increased levels of superoxide ions and hydroperoxides were observed in HD cybrids upon 3-NP or STS treatment. 3-NP-evoked apoptosis in HD cybrids involved cytochrome c and AIF release from mitochondria, which was associated with mitochondrial Bax translocation. CTR cybrids subjected to 3-NP showed increased mitochondrial Bax and Bim levels and the release of AIF, but not cytochrome c, suggesting a different mode of cell death, linked to the loss of membrane integrity. Additionally, increased mitochondrial Bim and Bak levels, and a slight release of cytochrome c in untreated HD cybrids may help to explain their moderate susceptibility to mitochondrial-dependent apoptosis
    2010Journal article Open access Show more
  • 2003Journal article Open access Show more