Tyrphostin A9 protects axons in experimental autoimmune encephalomyelitis through activation of ERKs.
Life Sci
; 294: 120383, 2022 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-35143827
ABSTRACT
AIMS:
Small molecule compound tyrphostin A9 (A9), an inhibitor of platelet-derived growth factor (PDGF) receptor, was previously reported by our group to stimulate extracellular signal-regulated kinase 1 (ERK1) and 2 (ERK2) in neuronal cells in a PDGF receptor-irrelevant manner. The study aimed to investigate whether A9 could protect axons in experimental autoimmune encephalomyelitis through activation of ERKs. MAINMETHODS:
A9 treatment on the protection on neurite outgrowth in SH-SY5Y neuroblastoma cells and primary substantia nigra neuron cultures from the neurotoxin MPP+ were analyzed. Then, clinical symptoms as well as ERK1/2 activation, axonal protection induction, and the abundance increases of the regeneration biomarker GAP-43 in the CNS in the relapsing-remitting experimental autoimmune encephalomyelitis (EAE) model were verified. KEYFINDINGS:
A9 treatment could stimulate neurite outgrowth in SH-SY5Y neuroblastoma cells and protect primary substantia nigra neuron cultures from the neurotoxin MPP+. In the relapsing-remitting EAE model, oral administration of A9 successfully ameliorated clinical symptoms, activated ERK1/2, induced axonal protection, and increased the abundance of the regeneration biomarker GAP-43 in the CNS. Interestingly, gene deficiency of ERK1 or ERK2 disrupted the beneficial effects of A9 in MOG-35-55-induced EAE.SIGNIFICANCE:
These results demonstrated that small molecule compounds that stimulate persistent ERK activation in vitro and in vivo may be useful in protective or restorative treatment for neurodegenerative diseases.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Axônios
/
Regulação da Expressão Gênica
/
Tirfostinas
/
MAP Quinases Reguladas por Sinal Extracelular
/
Modelos Animais de Doenças
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Encefalomielite Autoimune Experimental
/
Neuroblastoma
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Life Sci
Ano de publicação:
2022
Tipo de documento:
Article