Neurotrophic factor alpha 1 gene therapy in Alzheimer’s disease: scope and advancements

Alzheimer’s disease (AD) is the leading cause of dementia, accounting for 60–80% of all cases globally. Hallmark pathologies of AD include the accumulation of amyloid β peptide and phosphorylated tau, leading to neuronal circuit dysfunction, defective axonal transport, and neurotransmitter system (N...

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Main Authors: Ammara Shaikh, Fairus Ahmad, Seong Lin Teoh, Jaya Kumar, Mohamad Fairuz Yahaya
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Molecular Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnmol.2025.1518868/full
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author Ammara Shaikh
Fairus Ahmad
Seong Lin Teoh
Jaya Kumar
Mohamad Fairuz Yahaya
author_facet Ammara Shaikh
Fairus Ahmad
Seong Lin Teoh
Jaya Kumar
Mohamad Fairuz Yahaya
author_sort Ammara Shaikh
collection DOAJ
description Alzheimer’s disease (AD) is the leading cause of dementia, accounting for 60–80% of all cases globally. Hallmark pathologies of AD include the accumulation of amyloid β peptide and phosphorylated tau, leading to neuronal circuit dysfunction, defective axonal transport, and neurotransmitter system (NTS) abnormalities. Disruptions in acetylcholine, GABA, dopamine, serotonin, and glutamate levels, as well as the loss of cholinergic, GABAergic, and monoaminergic neurons, contribute to the progression of AD. Additionally, neurotrophic factors like brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are significantly reduced in AD, impacting neuronal health and synaptic integrity. This review highlights the emerging role of neurotrophic factor alpha 1 (NF-α1), also known as carboxypeptidase E, in AD. NF-α1 shows neuroprotective and neurogenesis-promoting properties, offering potential for therapeutic interventions. The review compares NF-α1 gene therapy with other neurotrophin-based treatments, providing insights into its efficacy in AD management.
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issn 1662-5099
language English
publishDate 2025-04-01
publisher Frontiers Media S.A.
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series Frontiers in Molecular Neuroscience
spelling doaj-art-bd27557637d3495b8aa804ee3ad907182025-08-20T03:04:35ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992025-04-011810.3389/fnmol.2025.15188681518868Neurotrophic factor alpha 1 gene therapy in Alzheimer’s disease: scope and advancementsAmmara Shaikh0Fairus Ahmad1Seong Lin Teoh2Jaya Kumar3Mohamad Fairuz Yahaya4Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, MalaysiaDepartment of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, MalaysiaDepartment of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, MalaysiaDepartment of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, MalaysiaDepartment of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, MalaysiaAlzheimer’s disease (AD) is the leading cause of dementia, accounting for 60–80% of all cases globally. Hallmark pathologies of AD include the accumulation of amyloid β peptide and phosphorylated tau, leading to neuronal circuit dysfunction, defective axonal transport, and neurotransmitter system (NTS) abnormalities. Disruptions in acetylcholine, GABA, dopamine, serotonin, and glutamate levels, as well as the loss of cholinergic, GABAergic, and monoaminergic neurons, contribute to the progression of AD. Additionally, neurotrophic factors like brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are significantly reduced in AD, impacting neuronal health and synaptic integrity. This review highlights the emerging role of neurotrophic factor alpha 1 (NF-α1), also known as carboxypeptidase E, in AD. NF-α1 shows neuroprotective and neurogenesis-promoting properties, offering potential for therapeutic interventions. The review compares NF-α1 gene therapy with other neurotrophin-based treatments, providing insights into its efficacy in AD management.https://www.frontiersin.org/articles/10.3389/fnmol.2025.1518868/fullAlzheimer’s diseaseamyloid β peptideneurotransmitter system (NTS) abnormalitiesneurotrophic factor alpha 1 (NF-α1)carboxypeptidase Egene therapy in AD
spellingShingle Ammara Shaikh
Fairus Ahmad
Seong Lin Teoh
Jaya Kumar
Mohamad Fairuz Yahaya
Neurotrophic factor alpha 1 gene therapy in Alzheimer’s disease: scope and advancements
Frontiers in Molecular Neuroscience
Alzheimer’s disease
amyloid β peptide
neurotransmitter system (NTS) abnormalities
neurotrophic factor alpha 1 (NF-α1)
carboxypeptidase E
gene therapy in AD
title Neurotrophic factor alpha 1 gene therapy in Alzheimer’s disease: scope and advancements
title_full Neurotrophic factor alpha 1 gene therapy in Alzheimer’s disease: scope and advancements
title_fullStr Neurotrophic factor alpha 1 gene therapy in Alzheimer’s disease: scope and advancements
title_full_unstemmed Neurotrophic factor alpha 1 gene therapy in Alzheimer’s disease: scope and advancements
title_short Neurotrophic factor alpha 1 gene therapy in Alzheimer’s disease: scope and advancements
title_sort neurotrophic factor alpha 1 gene therapy in alzheimer s disease scope and advancements
topic Alzheimer’s disease
amyloid β peptide
neurotransmitter system (NTS) abnormalities
neurotrophic factor alpha 1 (NF-α1)
carboxypeptidase E
gene therapy in AD
url https://www.frontiersin.org/articles/10.3389/fnmol.2025.1518868/full
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AT fairusahmad neurotrophicfactoralpha1genetherapyinalzheimersdiseasescopeandadvancements
AT seonglinteoh neurotrophicfactoralpha1genetherapyinalzheimersdiseasescopeandadvancements
AT jayakumar neurotrophicfactoralpha1genetherapyinalzheimersdiseasescopeandadvancements
AT mohamadfairuzyahaya neurotrophicfactoralpha1genetherapyinalzheimersdiseasescopeandadvancements