Probing into low-density lipoprotein receptor-related protein (LPR)-1-independent peptide transcytosis mechanisms

魁北克大学分子肿瘤学实验室在Borhane Annabi教授的指导下，与总部位于蒙特利尔的Angiochem公司合作，Angiochem公司以其适用于突破性药物的独特合成策略而闻名，这些药物优化为跨越血脑屏障(BBB)。这项技术将有助于更好地了解涉及中枢神经系统和大脑相关疾病的分子和细胞过程。本项目将研究细胞内低密度脂蛋白受体相关蛋白(LRP)-1受体依赖和独立途径的分子机制。这些途径开辟了各种各样的原始和复杂的分子策略，以探索新的和原始的分子和细胞过程，涉及到血管生成和低氧(低氧水平)对细胞和组织的影响等过程。目前提出的合作项目旨在确定和研究可能参与Angiopep运输的替代受体和/或相互作用的分子伙伴。这将增加对LRP-1运输机制的基本了解，使新的化学实体能够针对关键的细胞过程，如那些参与不受控制的致癌细胞增殖、细胞生存的过程，以及那些涉及肿瘤相关血管生成和脑相关疾病的机制。预期的好处将有助于加拿大工业和UQAM，在描述的联合研发活动中正在调查的目标领域预计将利用一种突破性的平台技术，使生物活性分子能够通过BBB进行生理运输。因此，Angiochem目前将自己定位为该领域的领导者。在学术上，UQAM的直接好处包括宝贵的培训机会、增加就业以及将令人振奋的工业伙伴关系固定在蒙特利尔地区。从科学上讲，UQAM的科学系将从这种积极的合作伙伴关系中获得更高的知名度，从而极大地受益于此。

The Laboratory of Molecular Oncology at the Université du Québec à Montréal (UQAM) and under the direction of Professor Borhane Annabi is partnering with AngioChem a Montreal-based company reknown for its unique synthetic strategies applicable to breakthrough pharmacological agents that are optimized to cross the blood-brain barrier (BBB). Such technology will help to better understand molecular and cellular processes involved in central nervous system and brain-related disorders. The current project will investigate the molecular mechanisms involved in intracellular low-density lipoprotein receptor-related protein (LRP)-1 receptor-dependent and independent pathways. Such pathways open up a wide variety of original and sophisticated molecular strategies to explore new and original molecular and cellular processes involved in processes such as angiogenesis and impact of hypoxia (low oxygen levels) on cells and tissues. The current proposed collaborative project is designed to identify and investigate the alternate receptors and/or interacting molecular partners that could be involved in the transport of Angiopeps. This will result in an increased fundamental understanding of the LRP-1 transport mechanisms that will enable novel chemical entities to target critical cellular processes such as those involved in uncontrolled carcinogenic cell proliferation, cell survival, as well as those mechanisms involved in tumour-associated angiogenesis, and in brain-related disorders. The expected benefits will help to accrue to Canadian industry and to UQAM, the targeted areas under investigation in the described joint research and development activities are expected to leverage a breakthrough platform technology enabling physiological transport of bioactive molecules across the BBB. As such, AngioChem currently positions itself as the leader in this field. Academically, the direct benefits to UQAM include valuable training opportunities, increased employment as well as anchoring exciting industrial partnerships to the Montreal region. Scientifically, UQAM's Faculty of Sciences will enormously benefit of increased visibility from such an active partnership.