Unlocking Alzheimer's Disease: The Role of BDNF Signaling in Neuropathology and Treatment.

IF 3.3 4区医学 Q2 NEUROSCIENCES

NeuroMolecular Medicine Pub Date : 2025-05-17 DOI:10.1007/s12017-025-08857-x

Saad Misfer Alqahtani, Hayder M Al-Kuraishy, Ali I Al Gareeb, Ali K Albuhadily, Athanasios Alexiou, Marios Papadakis, Loah R Hemeda, Safaa A Faheem, Gaber El-Saber Batiha

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Abstract

Alzheimer's disease (AD) remains one of the most debilitating neurodegenerative disorders, with its pathological hallmark being progressive cognitive decline and memory loss. Recent research has illuminated the crucial role of the brain-derived neurotrophic factor (BDNF) in the central nervous system (CNS), highlighting its impact on neurogenesis, synaptic plasticity, and neuronal survival. Dysregulation of the BDNF signaling axis, particularly the imbalance between its precursor form and mature BDNF, is strongly implicated in the pathophysiology of AD. This review explores the molecular mechanisms through which BDNF modulates AD neuropathology and presents novel therapeutic strategies to activate BDNF signaling. We focus on the potential of BDNF activators, such as TrkB agonists and mimetic molecules, to restore synaptic function and ameliorate cognitive deficits in AD. Furthermore, we examine the challenges in translating these findings into clinical practice, including issues with blood-brain barrier penetration and the need for precise receptor targeting. The review emphasizes the therapeutic potential of repurposed drugs, including statins and metformin, in enhancing BDNF signaling and offers new insights into the future of AD treatment. Ultimately, this work provides a compelling argument for BDNF-based therapies as a promising avenue for mitigating the cognitive decline associated with Alzheimer's disease, signaling a hopeful direction for future research and clinical trials.

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解锁阿尔茨海默病：BDNF信号在神经病理学和治疗中的作用。

阿尔茨海默病（AD）仍然是最使人衰弱的神经退行性疾病之一，其病理特征是进行性认知能力下降和记忆丧失。最近的研究已经阐明了脑源性神经营养因子（BDNF）在中枢神经系统（CNS）中的重要作用，强调了它对神经发生、突触可塑性和神经元存活的影响。BDNF信号轴的失调，特别是其前体形式和成熟BDNF之间的不平衡，与AD的病理生理密切相关。本文探讨了BDNF调节AD神经病理的分子机制，并提出了激活BDNF信号传导的新治疗策略。我们关注BDNF激活剂的潜力，如TrkB激动剂和模拟分子，以恢复突触功能和改善阿尔茨海默病的认知缺陷。此外，我们研究了将这些发现转化为临床实践的挑战，包括血脑屏障穿透问题和精确受体靶向的需要。该综述强调了包括他汀类药物和二甲双胍在内的重组药物在增强BDNF信号传导方面的治疗潜力，并为阿尔茨海默病治疗的未来提供了新的见解。最终，这项工作为bdnf为基础的治疗提供了一个令人信服的论据，作为缓解阿尔茨海默病相关认知能力下降的有希望的途径，为未来的研究和临床试验指明了一个有希望的方向。

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

NeuroMolecular Medicine 医学-神经科学

CiteScore

7.10

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： NeuroMolecular Medicine publishes cutting-edge original research articles and critical reviews on the molecular and biochemical basis of neurological disorders. Studies range from genetic analyses of human populations to animal and cell culture models of neurological disorders. Emerging findings concerning the identification of genetic aberrancies and their pathogenic mechanisms at the molecular and cellular levels will be included. Also covered are experimental analyses of molecular cascades involved in the development and adult plasticity of the nervous system, in neurological dysfunction, and in neuronal degeneration and repair. NeuroMolecular Medicine encompasses basic research in the fields of molecular genetics, signal transduction, plasticity, and cell death. The information published in NEMM will provide a window into the future of molecular medicine for the nervous system.