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• W2893889762 abstract "We previously reported up-regulation of tigarb (the zebrafish orthologue of human TIGAR, TP53 – Induced Glycolysis and Apoptosis Regulator) in a zebrafish pink1−/− model of Parkinson’s disease (PD). Genetic inactivation of tigarb led to the rescue of dopaminergic neurons and mitochondrial function in pink−/− zebrafish. The aim of this study was to determine the relevance of TIGAR for human PD, investigate its disease specificity and identify relevant upstream and downstream mechanisms. TIGAR Immunohistochemistry, using a range of antibodies, was undertaken for detailed assessment of TIGAR in formalin-fixed, paraffin-embedded tissue from post mortem brains of PD patients and other neurodegenerative disorders (n = 10 controls, 10 PD cases, 10 dementia with Lewy bodies, 5 motor neurone disease (MND), 3 multiple system atrophy (MSA)) and complemented by immunohistochemistry for p53, hexokinase I (HK-I) and hexokinase II (HK-II; n = 4 control, 4 PD, and 4 dementia with Lewy bodies). TIGAR was detected in Lewy bodies and Lewy neurites in the substantia nigra of sporadic PD and Dementia with Lewy bodies (DLB) patients. Staining of adjacent sections and double staining confirmed the presence of TIGAR alongside alpha-synuclein in these LB and neurites. In contrast, TIGAR-positive aggregates were not seen in cortical Lewy bodies. TIGAR protein was also absent in both TDP-43-positive inclusions in MND and glial cytoplasmic inclusions in MSA. Subsequent investigation of the TIGAR-upstream regulator p53 and the downstream targets HK-I and HK-II in PD brains suggested a possible mild increase in HK-I. TIGAR protein, is present in SN Lewy bodies of both sporadic PD and DLB. The absence of TIGAR protein in the pathological inclusions of MND or MSA suggests disease specificity and further raises the possibility that TIGAR may be involved in PD pathogenesis." @default.
• W2893889762 created "2018-10-05" @default.
• W2893889762 creator A5025748762 @default.
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• W2893889762 date "2019-03-01" @default.
• W2893889762 modified "2023-09-27" @default.
• W2893889762 title "TIGAR inclusion pathology is specific for Lewy body diseases" @default.
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• W2893889762 doi "https://doi.org/10.1016/j.brainres.2018.09.032" @default.
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