Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, 70124 Bari, Italy.
Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, 70124 Bari, Italy.
Biomolecules. 2023 Jan 16;13(1):183. doi: 10.3390/biom13010183.
Type 2 diabetes (T2D) and Alzheimer's diseases (AD) represent major health issues that have reached alarming levels in the last decades. Although growing evidence demonstrates that AD is a significant comorbidity of T2D, and there is a ~1.4-2-fold increase in the risk of developing AD among T2D patients, the involvement of possible common triggers in the pathogenesis of these two diseases remains largely unknown. Of note, recent mechanistic insights suggest that lipotoxicity could represent the missing ring in the pathogenetic mechanisms linking T2D to AD. Indeed, obesity, which represents the main cause of lipotoxicity, has been recognized as a major risk factor for both pathological conditions. Lipotoxicity can lead to inflammation, insulin resistance, oxidative stress, ceramide and amyloid accumulation, endoplasmic reticulum stress, ferroptosis, and autophagy, which are shared biological events in the pathogenesis of T2D and AD. In the current review, we try to provide a critical and comprehensive view of the common molecular pathways activated by lipotoxicity in T2D and AD, attempting to summarize how these mechanisms can drive future research and open the way to new therapeutic perspectives.
2 型糖尿病（T2D）和阿尔茨海默病（AD）是两个主要的健康问题，在过去几十年中已经达到了令人担忧的水平。尽管越来越多的证据表明 AD 是 T2D 的一个重要合并症，并且 T2D 患者患 AD 的风险增加了 1.4-2 倍，但这两种疾病发病机制中可能存在共同触发因素仍知之甚少。值得注意的是，最近的机制研究表明，脂毒性可能是将 T2D 与 AD 联系起来的发病机制中缺失的一环。事实上，肥胖是脂毒性的主要原因，已被认为是这两种病理状况的主要危险因素。脂毒性可导致炎症、胰岛素抵抗、氧化应激、神经酰胺和淀粉样蛋白积累、内质网应激、铁死亡和自噬，这些都是 T2D 和 AD 发病机制中的共同生物学事件。在本综述中，我们试图提供一个关于 T2D 和 AD 中脂毒性激活的共同分子途径的批判性和全面的观点，试图总结这些机制如何能够推动未来的研究并为新的治疗前景开辟道路。
