Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Harlequin (Hq) mice develop ataxia due to an X-linked recessive mutation in the gene encoding apoptosis-inducing factor (Aif). Brain cells in Hq mice contain the modified base 8-hydroxydeoxyguanosine (8-OHdG), suggesting that the defect in Aif causes increased DNA oxidation in these cells. Because oxidative damage is mutagenic, Hq mice might suffer increased mutation in the brain. To examine this possibility, mutation in the brain was assessed using the Tg(betaA-G11PLAP) mouse model, which allows mutant cells to be visualized in tissue sections in situ. Hq mice exhibited more and larger patches of PLAP positive tissue in the brain. PLAP+ cells were observed in all areas of the brain. No increase in the number of PLAP+ cells was seen in three other tissues, suggesting that the effect of Aif deficiency on mutation was specific to brain.
 ...
PMID:Increased mutation in mice genetically predisposed to oxidative damage in the brain. 1549 40

Ataxia severity, cerebellar hemispheric blood flow (CHBF), ascorbate free radical (AFR), superoxide dismutase protein, superoxide scavenging activity, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in cerebrospinal fluid (CSF) were compared before and after an 8-week course of repetitive transcranial magnetic stimulation (rTMS) in 20 patients with spinocerebellar degenerations (SCD). SCD patients showed higher AFR, 8-OHdG, and superoxide scavenging activity than 19 controls. In SCD patients, AFR and ataxia severity declined, and CHBF increased after rTMS. As the SCD patients showed negative correlations between ataxia severity and CHBF or superoxide scavenging activity, the therapeutic mechanism of rTMS may involve decreased oxidative stress and increased CHBF.
 ...
PMID:Influence of repetitive transcranial magnetic stimulation on disease severity and oxidative stress markers in the cerebrospinal fluid of patients with spinocerebellar degeneration. 1584 14

A comparative evaluation is reported of pro-oxidant states in 82 patients with ataxia telangectasia (AT), Bloom syndrome (BS), Down syndrome (DS), Fanconi anemia (FA), Werner syndrome (WS), and xeroderma pigmentosum (XP) vs 98 control donors. These disorders display cancer proneness, and/or early aging, and/or other clinical features. The measured analytes were: (a) leukocyte and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), (b) blood glutathione (GSSG and GSH), (c) plasma glyoxal (Glx) and methylglyoxal (MGlx), and (d) some plasma antioxidants [uric acid (UA) and ascorbic acid (AA)]. Leukocyte 8-OHdG levels ranked as follows: WS>BS approximately FA approximately XP>DS approximately AT approximately controls. Urinary 8-OHdG levels were significantly increased in a total of 22 patients with BS, FA, or XP vs 47 controls. The GSSG:GSH ratio was significantly increased in patients with WS and in young (< or =15 years) patients with DS or with FA and decreased in older patients with DS or FA and in AT, BS, and XP patients. The plasma levels of Glx and/or MGlx were significantly increased in patients with WS, FA, and DS. The UA and AA levels were significantly increased in WS and DS patients, but not in AT, FA, BS, nor XP patients. Rationale for chemoprevention trials is discussed.
 ...
PMID:Different patterns of in vivo pro-oxidant states in a set of cancer- or aging-related genetic diseases. 1805 16

In a "proof-of-concept" study, we demonstrated that recombinant human erythropoietin (rhuEPO) increases frataxin levels in Friedreich's ataxia (FRDA) patients. We now report a 6-month open-label clinical pilot study of safety and efficacy of rhuEPO treatment in FRDA. Eight adult FRDA patients received 2.000 IU rhuEPO thrice a week subcutaneously. Clinical outcome measures included Ataxia Rating Scales. Frataxin levels and indicators for oxidative stress were assessed. Hematological parameters were monitored biweekly. Scores in Ataxia Rating Scales such as FARS (P = 0.0063) and SARA (P = 0.0045) improved significantly. Frataxin levels increased (P = 0.017) while indicators of oxidative stress such as urine 8-OHdG (P = 0.012) and peroxide levels decreased (P = 0.028). Increases in hematocrit requiring phlebotomies occurred in 4 of 8 patients. In this explorative open-label clinical pilot study, we found an evidence for clinical improvement together with a persistent increase of frataxin levels and a reduction of oxidative stress parameters in patients with FRDA receiving chronic treatment with rhuEPO. Safety monitoring with regular blood cell counts and parameters of iron metabolism is a potential limitation of this approach.
 ...
PMID:Neurological effects of recombinant human erythropoietin in Friedreich's ataxia: a clinical pilot trial. 1875 45

The nna1 gene mutation is associated with spontaneous degeneration of cerebellar Purkinje cells and germ cells in Ataxia and Male Sterility (AMS) mouse. Since nna1 is also expressed in hippocampal neurons, we investigated their vulnerability to hypoperfusion in AMS mouse. Eight-week-old male wild type (WT) and AMS mice were subjected to bilateral common carotid artery occlusion (BCCAO) for 10 min and sacrificed 1, 3, 7 and 28 days after BCCAO. Nissl staining revealed the neuronal cell loss and pyknotic change in the CA1 of AMS mice. TUNEL(+) apoptotic cells were found in the area at 7 days in AMS mice. Bcl-2 mRNA and protein in WT hippocampus were increased, while they were not increased in AMS. Bax mRNA was increased in AMS. Moreover, Bax activation was immunohistochemically demonstrated only in AMS at 3 and 7 days after BCCAO. An oxidative DNA damage marker, 8-hydroxydeoxyguanosine-positive cells were increased in both strains at 1 day; decreased in WT at 3 days but remained high in AMS. BCCAO increased glutathione, an antioxidant, in WT, but not in AMS at 3 days. The mRNA level of mitochondrial uncoupling protein 2, a regulator of oxidative stress, was increased only in WT at 1 day. Nna1 mRNA was similarly expressed in WT and AMS, but the protein was undetectable in AMS. Thus, our results indicate the increased vulnerability of hippocampal CA1 neurons of AMS mice to cerebral hypoperfusion could be due to an imbalance between oxidative stress and antioxidative defense system.
 ...
PMID:Increased vulnerability of hippocampal CA1 neurons to hypoperfusion in ataxia and male sterility (AMS) mouse. 2321 73