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Hippocampal delivery of neurotrophic factor-α1/carboxypeptidase E gene prevents neurodegeneration, amyloidosis, memory loss in Alzheimer’s Disease male mice
by
Xiao, Lan
, Yang, Xuyu
, Sharma, Vinay Kumar
, Abebe, Daniel
, Loh, Y. Peng
in
14/63
/ 38/109
/ 38/77
/ 42/41
/ 631/378
/ 631/443
/ 64/60
/ 82/51
/ 82/80
/ Alzheimer Disease - metabolism
/ Alzheimer's disease
/ Amnesia - metabolism
/ Amyloid beta-Peptides - metabolism
/ Amyloid beta-Protein Precursor - genetics
/ Amyloid beta-Protein Precursor - metabolism
/ Amyloid precursor protein
/ Amyloidosis
/ Amyloidosis - genetics
/ Amyloidosis - metabolism
/ Animals
/ Bcl-2 protein
/ Behavioral Sciences
/ Biological Psychology
/ Brain-derived neurotrophic factor
/ Carboxypeptidase E
/ Carboxypeptidase H - genetics
/ Carboxypeptidase H - metabolism
/ Cell survival
/ Cognitive ability
/ Disease Models, Animal
/ E protein
/ Fibroblast growth factor 2
/ Gene therapy
/ Hippocampus
/ Hippocampus - metabolism
/ Inflammation
/ Male
/ Medicine
/ Medicine & Public Health
/ Memory
/ Memory Disorders - genetics
/ Memory Disorders - metabolism
/ Memory Disorders - prevention & control
/ Mice
/ Mice, Transgenic
/ Mitophagy
/ Nerve Growth Factors - metabolism
/ Neurodegeneration
/ Neurodegenerative diseases
/ Neurodegenerative Diseases - metabolism
/ Neurosciences
/ Pattern recognition
/ Pharmacotherapy
/ Phosphorylation
/ Psychiatry
/ Tau protein
/ tau Proteins - genetics
/ tau Proteins - metabolism
2023
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Hippocampal delivery of neurotrophic factor-α1/carboxypeptidase E gene prevents neurodegeneration, amyloidosis, memory loss in Alzheimer’s Disease male mice
by
Xiao, Lan
, Yang, Xuyu
, Sharma, Vinay Kumar
, Abebe, Daniel
, Loh, Y. Peng
in
14/63
/ 38/109
/ 38/77
/ 42/41
/ 631/378
/ 631/443
/ 64/60
/ 82/51
/ 82/80
/ Alzheimer Disease - metabolism
/ Alzheimer's disease
/ Amnesia - metabolism
/ Amyloid beta-Peptides - metabolism
/ Amyloid beta-Protein Precursor - genetics
/ Amyloid beta-Protein Precursor - metabolism
/ Amyloid precursor protein
/ Amyloidosis
/ Amyloidosis - genetics
/ Amyloidosis - metabolism
/ Animals
/ Bcl-2 protein
/ Behavioral Sciences
/ Biological Psychology
/ Brain-derived neurotrophic factor
/ Carboxypeptidase E
/ Carboxypeptidase H - genetics
/ Carboxypeptidase H - metabolism
/ Cell survival
/ Cognitive ability
/ Disease Models, Animal
/ E protein
/ Fibroblast growth factor 2
/ Gene therapy
/ Hippocampus
/ Hippocampus - metabolism
/ Inflammation
/ Male
/ Medicine
/ Medicine & Public Health
/ Memory
/ Memory Disorders - genetics
/ Memory Disorders - metabolism
/ Memory Disorders - prevention & control
/ Mice
/ Mice, Transgenic
/ Mitophagy
/ Nerve Growth Factors - metabolism
/ Neurodegeneration
/ Neurodegenerative diseases
/ Neurodegenerative Diseases - metabolism
/ Neurosciences
/ Pattern recognition
/ Pharmacotherapy
/ Phosphorylation
/ Psychiatry
/ Tau protein
/ tau Proteins - genetics
/ tau Proteins - metabolism
2023
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Hippocampal delivery of neurotrophic factor-α1/carboxypeptidase E gene prevents neurodegeneration, amyloidosis, memory loss in Alzheimer’s Disease male mice
by
Xiao, Lan
, Yang, Xuyu
, Sharma, Vinay Kumar
, Abebe, Daniel
, Loh, Y. Peng
in
14/63
/ 38/109
/ 38/77
/ 42/41
/ 631/378
/ 631/443
/ 64/60
/ 82/51
/ 82/80
/ Alzheimer Disease - metabolism
/ Alzheimer's disease
/ Amnesia - metabolism
/ Amyloid beta-Peptides - metabolism
/ Amyloid beta-Protein Precursor - genetics
/ Amyloid beta-Protein Precursor - metabolism
/ Amyloid precursor protein
/ Amyloidosis
/ Amyloidosis - genetics
/ Amyloidosis - metabolism
/ Animals
/ Bcl-2 protein
/ Behavioral Sciences
/ Biological Psychology
/ Brain-derived neurotrophic factor
/ Carboxypeptidase E
/ Carboxypeptidase H - genetics
/ Carboxypeptidase H - metabolism
/ Cell survival
/ Cognitive ability
/ Disease Models, Animal
/ E protein
/ Fibroblast growth factor 2
/ Gene therapy
/ Hippocampus
/ Hippocampus - metabolism
/ Inflammation
/ Male
/ Medicine
/ Medicine & Public Health
/ Memory
/ Memory Disorders - genetics
/ Memory Disorders - metabolism
/ Memory Disorders - prevention & control
/ Mice
/ Mice, Transgenic
/ Mitophagy
/ Nerve Growth Factors - metabolism
/ Neurodegeneration
/ Neurodegenerative diseases
/ Neurodegenerative Diseases - metabolism
/ Neurosciences
/ Pattern recognition
/ Pharmacotherapy
/ Phosphorylation
/ Psychiatry
/ Tau protein
/ tau Proteins - genetics
/ tau Proteins - metabolism
2023
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Hippocampal delivery of neurotrophic factor-α1/carboxypeptidase E gene prevents neurodegeneration, amyloidosis, memory loss in Alzheimer’s Disease male mice
Journal Article
Hippocampal delivery of neurotrophic factor-α1/carboxypeptidase E gene prevents neurodegeneration, amyloidosis, memory loss in Alzheimer’s Disease male mice
2023
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Overview
Alzheimer’s Disease (AD) is a prevalent neurodegenerative disease characterized by tau hyperphosphorylation, Aβ1-42 aggregation and cognitive dysfunction. Therapeutic agents directed at mitigating tau aggregation and clearing Aβ1-42, and delivery of growth factor genes (BDNF, FGF2), have ameliorated cognitive deficits, but these approaches did not prevent or stop AD progression. Here we report that viral-(AAV) delivery of Neurotrophic Factor-α1/Carboxypeptidase E (NF-α1/CPE) gene in hippocampus at an early age prevented later development of cognitive deficits as assessed by Morris water maze and novel object recognition assays, neurodegeneration, and tau hyperphosphorylation in male 3xTg-AD mice. Additionally, amyloid precursor protein (APP) expression was reduced to near non-AD levels, and insoluble Aβ1-42 was reduced significantly. Pro-survival proteins: mitochondrial Bcl2 and Serpina3g were increased; and mitophagy inhibitor Plin4 and pro-inflammatory protein Card14 were decreased in AAV-NF-α1/CPE treated versus untreated AD mice. Thus NF-α1/CPE gene therapy targets many regulatory components to prevent cognitive deficits in 3xTg-AD mice and has implications as a new therapy to prevent AD progression by promoting cell survival, inhibiting APP overexpression and tau hyperphosphorylation.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 38/109
/ 38/77
/ 42/41
/ 631/378
/ 631/443
/ 64/60
/ 82/51
/ 82/80
/ Alzheimer Disease - metabolism
/ Amyloid beta-Peptides - metabolism
/ Amyloid beta-Protein Precursor - genetics
/ Amyloid beta-Protein Precursor - metabolism
/ Animals
/ Brain-derived neurotrophic factor
/ Carboxypeptidase H - genetics
/ Carboxypeptidase H - metabolism
/ Male
/ Medicine
/ Memory
/ Memory Disorders - metabolism
/ Memory Disorders - prevention & control
/ Mice
/ Nerve Growth Factors - metabolism
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