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

IF 3.5 3区医学 Q2 NEUROSCIENCES

Frontiers in Molecular Neuroscience Pub Date : 2025-04-01 eCollection Date: 2025-01-01 DOI:10.3389/fnmol.2025.1518868

Ammara Shaikh, Fairus Ahmad, Seong Lin Teoh, Jaya Kumar, Mohamad Fairuz Yahaya

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Abstract

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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神经营养因子α 1基因治疗阿尔茨海默病：范围和进展。

阿尔茨海默病（AD）是痴呆症的主要原因，占全球所有病例的60-80%。AD的标志性病理包括淀粉样蛋白β肽和磷酸化tau的积累，导致神经元回路功能障碍，轴突运输缺陷和神经递质系统（NTS）异常。乙酰胆碱、GABA、多巴胺、血清素和谷氨酸水平的破坏，以及胆碱能、GABA能和单胺能神经元的丧失，都有助于AD的进展。此外，脑源性神经营养因子（BDNF）和神经生长因子（NGF）等神经营养因子在AD中显著减少，影响神经元健康和突触完整性。这篇综述强调了神经营养因子α1 (NF-α1)，也被称为羧基肽酶E，在AD中的新作用。NF-α1具有神经保护和神经发生促进作用，具有潜在的治疗干预作用。该综述比较了NF-α1基因治疗与其他基于神经营养因子的治疗，为其在AD治疗中的疗效提供了见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Molecular Neuroscience NEUROSCIENCES-

CiteScore

5.70

自引率

2.10%

发文量

669

审稿时长

14 weeks

期刊介绍： Frontiers in Molecular Neuroscience is a first-tier electronic journal devoted to identifying key molecules, as well as their functions and interactions, that underlie the structure, design and function of the brain across all levels. The scope of our journal encompasses synaptic and cellular proteins, coding and non-coding RNA, and molecular mechanisms regulating cellular and dendritic RNA translation. In recent years, a plethora of new cellular and synaptic players have been identified from reduced systems, such as neuronal cultures, but the relevance of these molecules in terms of cellular and synaptic function and plasticity in the living brain and its circuits has not been validated. The effects of spine growth and density observed using gene products identified from in vitro work are frequently not reproduced in vivo. Our journal is particularly interested in studies on genetically engineered model organisms (C. elegans, Drosophila, mouse), in which alterations in key molecules underlying cellular and synaptic function and plasticity produce defined anatomical, physiological and behavioral changes. In the mouse, genetic alterations limited to particular neural circuits (olfactory bulb, motor cortex, cortical layers, hippocampal subfields, cerebellum), preferably regulated in time and on demand, are of special interest, as they sidestep potential compensatory developmental effects.