PUBLICATION
TIGAR inclusion pathology is specific for Lewy body diseases
- Authors
- Robles López, K.L., Simpson, J.E., Watson, L.C., Mortiboys, H., Hautbergue, G.M., Bandmann, O., Highley, J.R.
- ID
- ZDB-PUB-180930-4
- Date
- 2018
- Source
- Brain research 1706: 218-223 (Journal)
- Registered Authors
- Bandmann, Oliver
- Keywords
- Alpha-synuclein, Dementia with Lewy bodies, Lewy body, Parkinson’s disease, Substantia nigra, TIGAR
- MeSH Terms
-
- Aged
- Aged, 80 and over
- Apoptosis Regulatory Proteins/metabolism*
- Brain/metabolism
- Brain/pathology
- Dementia/metabolism
- Dementia/pathology
- Female
- Humans
- Immunohistochemistry/methods
- Inclusion Bodies/metabolism
- Lewy Bodies/metabolism
- Lewy Bodies/pathology
- Lewy Body Disease/metabolism*
- Lewy Body Disease/pathology
- Male
- Middle Aged
- Motor Neuron Disease/metabolism
- Motor Neuron Disease/pathology
- Multiple System Atrophy/metabolism
- Multiple System Atrophy/pathology
- Neurites/metabolism
- Neurites/pathology
- Neurons/metabolism
- Neurons/pathology
- Parkinson Disease/metabolism
- Parkinson Disease/pathology*
- Phosphoric Monoester Hydrolases/metabolism*
- Substantia Nigra/metabolism
- Substantia Nigra/pathology
- alpha-Synuclein/metabolism
- PubMed
- 30267647 Full text @ Brain Res.
Citation
Robles López, K.L., Simpson, J.E., Watson, L.C., Mortiboys, H., Hautbergue, G.M., Bandmann, O., Highley, J.R. (2018) TIGAR inclusion pathology is specific for Lewy body diseases. Brain research. 1706:218-223.
Abstract
Background We previously reported up-regulation of tigarb (the zebrafish analogue 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.
Materials and methods TIGAR Immunohistochemistry was undertaken for detailed assessment of TIGAR in post mortem brains of patients with PD and other neurodegenerative disorders and complemented by immunohistochemistry for p53, hexokinase I (HK-I) and hexokinase II (HK-II).
Results 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 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 motor neurone disease (MND) and glial cytoplasmic inclusions in multiple system atrophy (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-II.
Conclusions 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping