International Experimental CNS Injury & Repair (IECNSIR), University Hospital, Uppsala University, Uppsala, Sweden; Laboratory of Cerebrovascular Research, University Hospital, Uppsala University, Uppsala, Sweden.
School of Biomedical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
Int Rev Neurobiol. 2017;137:123-165. doi: 10.1016/bs.irn.2017.09.002. Epub 2017 Nov 6.
More than 5.5 million Americans of all ages are suffering from Alzheimer's disease (AD) till today for which no suitable therapy has been developed so far. Thus, there is an urgent need to explore novel therapeutic measures to contain brain pathology in AD. The hallmark of AD includes amyloid-beta peptide (AβP) deposition and phosphorylation of tau in AD brain. Recent evidences also suggest a marked decrease in neurotrophic factors in AD. Thus, exogenous supplement of neurotrophic factors could be one of the possible ways for AD therapy. Human postmortem brain in AD shows alterations in histamine receptors as well, indicating an involvement of the amine in AD-induced brain pathology. In this review, we focused on role of histamine 3 and 4 receptor-modulating drugs in the pathophysiology of AD. Moreover, antibodies to histamine and tau appear to be also beneficial in reducing brain pathology, blood-brain barrier breakdown, and edema formation in AD. Interestingly, TiO-nanowired delivery of cerebrolysin-a balanced composition of several neurotrophic factors attenuated AβP deposition and reduced tau phosphorylation in AD brain leading to neuroprotection. Coadministration of cerebrolysin with histamine antibodies or tau antibodies has further enhanced neuroprotection in AD. These novel observations strongly suggest a role of nanomedicine in AD that requires further investigation.
迄今为止，已有超过 550 万美国各年龄段的人患有阿尔茨海默病（AD），但目前尚未开发出合适的治疗方法。因此，迫切需要探索新的治疗措施来控制 AD 患者的大脑病理变化。AD 的特征包括淀粉样β肽（AβP）在 AD 大脑中的沉积和 tau 的磷酸化。最近的证据还表明 AD 患者神经生长因子明显减少。因此，外源性补充神经生长因子可能是 AD 治疗的方法之一。AD 患者死后大脑中的组织胺受体也发生改变，表明胺在 AD 诱导的大脑病理变化中起作用。在这篇综述中，我们重点关注了组胺 3 和 4 受体调节药物在 AD 病理生理学中的作用。此外，针对组织胺和 tau 的抗体似乎也有益于减少 AD 患者大脑病理变化、血脑屏障破坏和脑水肿的形成。有趣的是，TiO-纳米载体递送脑活素——几种神经营养因子的平衡组合，可减轻 AD 大脑中的 AβP 沉积并减少 tau 磷酸化，从而起到神经保护作用。脑活素与组织胺抗体或 tau 抗体联合使用可进一步增强 AD 的神经保护作用。这些新的观察结果强烈表明纳米医学在 AD 中的作用，需要进一步研究。
