Class I and II histone deacetylase expression is not altered in human amyotrophic lateral sclerosis: Neuropathological and positron emission tomography molecular neuroimaging evidence.
Muscle Nerve
; 60(4): 443-452, 2019 10.
Article
em En
| MEDLINE
| ID: mdl-31241177
ABSTRACT
INTRODUCTION:
There is an unmet need for mechanism-based biomarkers and effective disease modifying treatments in amyotrophic lateral sclerosis (ALS). Previous findings have provided evidence that histone deacetylases (HDAC) are altered in ALS, providing a rationale for testing HDAC inhibitors as a therapeutic option.METHODS:
We measured class I and II HDAC protein and transcript levels together with acetylation levels of downstream substrates by using Western blotting in postmortem tissue of ALS and controls. [11 C]Martinostat, a novel HDAC positron emission tomography ligand, was also used to assess in vivo brain HDAC alterations in patients with ALS and healthy controls (HC).RESULTS:
There was no significant difference in HDAC levels between patients with ALS and controls as measured by Western blotting and reverse-transcription quantitative polymerase chain reaction. Similarly, no differences were detected in [11 C]Martinostat-positron emission tomography uptake in ALS participants compared with HCs.DISCUSSION:
These findings provide evidence that alterations in HDAC isoforms are not a dominant pathological feature at the bulk tissue level in ALS.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Medula Espinal
/
Histona Desacetilases
/
Esclerose Lateral Amiotrófica
/
Córtex Motor
Tipo de estudo:
Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
Limite:
Aged80
Idioma:
En
Revista:
Muscle Nerve
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos