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基于神经营养因子的神经系统疾病药理学方法。

Neurotrophic factor-based pharmacological approaches in neurological disorders.

作者信息

Alfonsetti Margherita, d'Angelo Michele, Castelli Vanessa

机构信息

Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.

出版信息

Neural Regen Res. 2023 Jun;18(6):1220-1228. doi: 10.4103/1673-5374.358619.

Abstract

Aging is a physiological event dependent on multiple pathways that are linked to lifespan and processes leading to cognitive decline. This process represents the major risk factor for aging-related diseases such as Alzheimer's disease, Parkinson's disease, and ischemic stroke. The incidence of all these pathologies increases exponentially with age. Research on aging biology has currently focused on elucidating molecular mechanisms leading to the development of those pathologies. Cognitive deficit and neurodegeneration, common features of aging-related pathologies, are related to the alteration of the activity and levels of neurotrophic factors, such as brain-derived neurotrophic factor, nerve growth factor, and glial cell-derived neurotrophic factor. For this reason, treatments that modulate neurotrophin levels have acquired a great deal of interest in preventing neurodegeneration and promoting neural regeneration in several neurological diseases. Those treatments include both the direct administration of neurotrophic factors and the induced expression with viral vectors, neurotrophins' binding with biomaterials or other molecules to increase their bioavailability but also cell-based therapies. Considering neurotrophins' crucial role in aging pathologies, here we discuss the involvement of several neurotrophic factors in the most common brain aging-related diseases and the most recent therapeutic approaches that provide direct and sustained neurotrophic support.

摘要

衰老 是一种依赖于多种途径的生理事件,这些途径与寿命以及导致认知衰退的过程相关联。这一过程是阿尔茨海默病、帕金森病和缺血性中风等衰老相关疾病的主要风险因素。所有这些疾病的发病率都随年龄呈指数增长。目前,衰老生物学研究主要集中在阐明导致这些疾病发生发展的分子机制。认知缺陷和神经退行性变是衰老相关疾病的常见特征,与神经营养因子(如脑源性神经营养因子、神经生长因子和胶质细胞源性神经营养因子)的活性和水平改变有关。因此,调节神经营养因子水平的治疗方法在预防多种神经疾病中的神经退行性变和促进神经再生方面引起了广泛关注。这些治疗方法包括直接给予神经营养因子、用病毒载体诱导表达、使神经营养因子与生物材料或其他分子结合以提高其生物利用度,以及基于细胞的疗法。鉴于神经营养因子在衰老相关疾病中的关键作用,本文我们将讨论几种神经营养因子在最常见的脑衰老相关疾病中的作用,以及提供直接和持续神经营养支持的最新治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca4f/9838155/c2dcc8c603d8/NRR-18-1220-g001.jpg

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