Mitra Sumonto, Behbahani Homira, Eriksdotter Maria
Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
Division of Neurogeriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Solna, Sweden.
Front Neurosci. 2019 Feb 5;13:38. doi: 10.3389/fnins.2019.00038. eCollection 2019.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with abnormal protein modification, inflammation and memory impairment. Aggregated amyloid beta (Aβ) and phosphorylated tau proteins are medical diagnostic features. Loss of memory in AD has been associated with central cholinergic dysfunction in basal forebrain, from where the cholinergic circuitry projects to cerebral cortex and hippocampus. Various reports link AD progression with declining activity of cholinergic neurons in basal forebrain. The neurotrophic molecule, nerve growth factor (NGF), plays a major role in the maintenance of cholinergic neurons integrity and function, both during development and adulthood. Numerous studies have also shown that NGF contributes to the survival and regeneration of neurons during aging and in age-related diseases such as AD. Changes in neurotrophic signaling pathways are involved in the aging process and contribute to cholinergic and cognitive decline as observed in AD. Further, gradual dysregulation of neurotrophic factors like NGF and brain derived neurotrophic factor (BDNF) have been reported during AD development thus intensifying further research in targeting these factors as disease modifying therapies against AD. Today, there is no cure available for AD and the effects of the symptomatic treatment like cholinesterase inhibitors (ChEIs) and memantine are transient and moderate. Although many AD treatment studies are being carried out, there has not been any breakthrough and new therapies are thus highly needed. Long-term effective therapy for alleviating cognitive impairment is a major unmet need. Discussion and summarizing the new advancements of using NGF as a potential therapeutic implication in AD are important. In summary, the intent of this review is describing available experimental and clinical data related to AD therapy, priming to gain additional facts associated with the importance of NGF for AD treatment, and encapsulated cell biodelivery (ECB) as an efficient tool for NGF delivery.
阿尔茨海默病(AD)是一种进行性神经退行性疾病,与异常蛋白质修饰、炎症和记忆障碍有关。淀粉样β蛋白(Aβ)聚集和磷酸化tau蛋白是医学诊断特征。AD患者的记忆丧失与基底前脑的中枢胆碱能功能障碍有关,胆碱能神经回路从基底前脑投射到大脑皮层和海马体。各种报告将AD的进展与基底前脑胆碱能神经元活性下降联系起来。神经营养分子神经生长因子(NGF)在发育和成年期维持胆碱能神经元的完整性和功能方面发挥着重要作用。许多研究还表明,NGF有助于衰老过程中以及AD等与年龄相关疾病中神经元的存活和再生。神经营养信号通路的变化参与衰老过程,并导致AD中观察到的胆碱能和认知功能下降。此外,在AD发展过程中,已报道神经营养因子如NGF和脑源性神经营养因子(BDNF)逐渐失调,从而加强了针对这些因子作为AD疾病修饰疗法的进一步研究。如今,AD尚无治愈方法,胆碱酯酶抑制剂(ChEIs)和美金刚等对症治疗的效果是短暂且适度的。尽管正在进行许多AD治疗研究,但尚未有任何突破,因此迫切需要新的疗法。缓解认知障碍的长期有效疗法是一个尚未满足的主要需求。讨论和总结将NGF用作AD潜在治疗方法的新进展很重要。总之,本综述的目的是描述与AD治疗相关的现有实验和临床数据,以获取与NGF对AD治疗重要性相关的更多事实,并将封装细胞生物递送(ECB)作为NGF递送的有效工具。