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Fibroblast growth factor 10 ameliorates neurodegeneration in mouse and cellular models of Alzheimer's disease via reducing tau hyperphosphorylation and neuronal apoptosis.
Guo, Kaiming; Huang, Wenting; Chen, Kun; Huang, Pengkai; Peng, Wenshuo; Shi, Ruiqing; He, Tao; Zhang, Mulan; Wang, Hao; Hu, Jian; Wang, Xinshi; Shentu, Yangping; Xu, Huiqin; Lin, Li.
Afiliação
  • Guo K; School of Pharmaceutical Sciences, Wenzhou Medical University, University-town, Wenzhou, China.
  • Huang W; Oujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain Health, Wenzhou, China.
  • Chen K; The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • Huang P; School of Pharmaceutical Sciences, Wenzhou Medical University, University-town, Wenzhou, China.
  • Peng W; Jinhua Maternity and Child Health Care Hospital, Jinhua, China.
  • Shi R; School of Pharmaceutical Sciences, Wenzhou Medical University, University-town, Wenzhou, China.
  • He T; School of Pharmaceutical Sciences, Wenzhou Medical University, University-town, Wenzhou, China.
  • Zhang M; The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • Wang H; School of Pharmaceutical Sciences, Wenzhou Medical University, University-town, Wenzhou, China.
  • Hu J; The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • Wang X; The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • Shentu Y; School of Pharmaceutical Sciences, Wenzhou Medical University, University-town, Wenzhou, China.
  • Xu H; Oujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain Health, Wenzhou, China.
  • Lin L; School of Pharmaceutical Sciences, Wenzhou Medical University, University-town, Wenzhou, China.
Aging Cell ; 22(9): e13937, 2023 09.
Article em En | MEDLINE | ID: mdl-37503695
Alzheimer's disease (AD) is characterized with senile plaques formed by Aß deposition, and neurofibrillary tangles composed of hyperphosphorylated tau protein, which ultimately lead to cognitive impairment. Despite the heavy economic and life burdens faced by the patients with AD, effective treatments are still lacking. Previous studies have reported the neuroprotective effects of FGF10 in CNS diseases, but its role in AD remains unclear. In this study, we demonstrated that FGF10 levels were reduced in the serum of AD patients, as well as in the brains of 3xTg-AD mice and APPswe-transfected HT22 cells, suggesting a close relationship between FGF10 and AD. Further investigations revealed that intranasal delivery of FGF10 improved cognitive functions in 3xTg-AD mice. Additionally, FGF10 treatment reduced tau hyperphosphorylation and neuronal apoptosis, thereby mitigating neuronal cell damage and synaptic deficits in the cortex and hippocampus of 3xTg-AD mice, as well as APPswe-transfected HT22 cells. Furthermore, we evaluated the therapeutic potential of FGF10 gene delivery for treating AD symptoms and pathologies. Tail vein delivery of the FGF10 gene using AAV9 improved cognitive and neuronal functions in 3xTg-AD mice. Similarly, endogenous FGF10 overexpression ameliorated tau hyperphosphorylation and neuronal apoptosis in the cortex and hippocampus of 3xTg-AD mice. Importantly, we confirmed that the FGFR2/PI3K/AKT signaling pathway was activated following intranasal FGF10 delivery and AAV9-mediated FGF10 gene delivery in 3xTg-AD mice and APPswe-transfected HT22 cells. Knockdown of FGFR2 attenuated the protective effect of FGF10. Collectively, these findings suggest that intranasal delivery of FGF10 and AAV9-mediated FGF10 gene delivery could be a promising disease-modifying therapy for AD.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Alzheimer Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Alzheimer Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article