Castilla-Cortázar Inma, Aguirre Gabriel A, Femat-Roldán Giovana, Martín-Estal Irene, Espinosa Luis
Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Ave. Morones Prieto 3000, 64710, Monterrey, N.L., Mexico.
Fundación de Investigación HM Hospitales, Madrid, Spain.
J Transl Med. 2020 Feb 11;18(1):70. doi: 10.1186/s12967-020-02223-0.
Parkinson's disease (PD) is a neurodegenerative disorder that results in the death of dopaminergic neurons within the substantia nigra pars compacta and the reduction in dopaminergic control over striatal output neurons, leading to a movement disorder most commonly characterized by akinesia or bradykinesia, rigidity and tremor. Also, PD is less frequently depicted by sensory symptoms (pain and tingling), hyposmia, sleep alterations, depression and anxiety, and abnormal executive and working memory related functions. On the other hand, insulin-like growth factor 1 (IGF-1) is an endocrine, paracrine and autocrine hormone with several functions including tissue growth and development, insulin-like activity, proliferation, pro-survival, anti-aging, antioxidant and neuroprotection, among others. Herein this review tries to summarize all experimental and clinical data to understand the pathophysiology and development of PD, as well as its clear association with IGF-1, supported by several lines of evidence: (1) IGF-1 decreases with age, while aging is the major risk for PD establishment and development; (2) numerous basic and translational data have appointed direct protective and homeostasis IGF-1 roles in all brain cells; (3) estrogens seem to confer women strong protection to PD via IGF-1; and (4) clinical correlations in PD cohorts have confirmed elevated IGF-1 levels at the onset of the disease, suggesting an ongoing compensatory or "fight-to-injury" mechanism.
帕金森病(PD)是一种神经退行性疾病,它导致黑质致密部内的多巴胺能神经元死亡,以及对纹状体输出神经元的多巴胺能控制减弱,从而引发一种运动障碍,其最常见的特征是运动不能或运动迟缓、僵硬和震颤。此外,PD较少表现为感觉症状(疼痛和刺痛)、嗅觉减退、睡眠改变、抑郁和焦虑,以及与执行和工作记忆相关的异常功能。另一方面,胰岛素样生长因子1(IGF-1)是一种内分泌、旁分泌和自分泌激素,具有多种功能,包括组织生长和发育、胰岛素样活性、增殖、促存活、抗衰老、抗氧化和神经保护等。在本综述中,试图总结所有实验和临床数据,以了解PD的病理生理学和发展,以及其与IGF-1的明确关联,这得到了多方面证据的支持:(1)IGF-1水平随年龄下降,而衰老却是PD发生和发展的主要风险因素;(2)众多基础和转化研究数据表明IGF-1在所有脑细胞中具有直接的保护和稳态维持作用;(3)雌激素似乎通过IGF-1赋予女性对PD的强大保护作用;(4)PD队列中的临床相关性研究证实,在疾病发作时IGF-1水平升高,这表明存在一种持续的代偿或“对抗损伤”机制。