Victorino Daniella Balduino, Nejm Mariana, Guimarães-Marques Marcia, Scorza Fulvio Alexandre, Scorza Carla Alessandra
Discipline of Neuroscience, Department of Neurology and Neurosurgery, Paulista Medical School, Federal University of São Paulo, Pedro de Toledo 669, 1st Floor, São Paulo, SP, 04039-032, Brazil.
Pharmaceut Med. 2021 Jan;35(1):11-19. doi: 10.1007/s40290-020-00374-5. Epub 2021 Jan 7.
The global burden of chronic disorders such as Parkinson's disease (PD) has rapidly increased over recent decades. Despite an increasing understanding of PD pathophysiology, there are no effective therapies capable of stopping or slowing the progression of this neurological condition. It has been suggested that type 2 diabetes mellitus (T2DM) may be a risk factor for PD and comorbid T2DM may worsen PD symptoms, as well as accelerate neurodegeneration. In fact, the similar pathological mechanisms shared by PD and T2DM have inspired several studies on the therapeutic potential of T2DM drugs against PD, among which glucagon-like peptide-1 receptor (GLP-1R) agonists are promising candidates. Here, we highlight the mechanisms linking T2DM and PD, as well as the links between insulin resistance (IR) and PD patients' risk of developing cognitive deficits. We also briefly review the effects of GLP-1R agonists on PD and discuss how the successful use of these substances in preclinical models of PD has paved the way for PD clinical trials. We further discuss how recent evidence on the beneficial effects of dulaglutide on cognitive function of T2DM patients may have important implications for PD drug repurposing.
近几十年来，帕金森病（PD）等慢性疾病的全球负担迅速增加。尽管对PD病理生理学的认识不断加深，但目前尚无有效的疗法能够阻止或减缓这种神经疾病的进展。有人提出，2型糖尿病（T2DM）可能是PD的一个风险因素，合并T2DM可能会使PD症状恶化，并加速神经退行性变。事实上，PD和T2DM共有的相似病理机制激发了多项关于T2DM药物治疗PD潜力的研究，其中胰高血糖素样肽-1受体（GLP-1R）激动剂是很有前景的候选药物。在此，我们重点介绍T2DM与PD之间的联系机制，以及胰岛素抵抗（IR）与PD患者发生认知缺陷风险之间的联系。我们还简要回顾了GLP-1R激动剂对PD的影响，并讨论了这些物质在PD临床前模型中的成功应用如何为PD临床试验铺平了道路。我们进一步讨论了度拉鲁肽对T2DM患者认知功能有益影响的最新证据可能对PD药物重新利用具有重要意义。
