Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Mol Neurobiol. 2024 Aug;61(8):5002-5026. doi: 10.1007/s12035-023-03901-y. Epub 2023 Dec 29.
Pyruvate kinase M2 (PKM2) is a key rate-limiting enzyme in glycolysis. It is well known that PKM2 plays a vital role in the proliferation of tumor cells. However, PKM2 can also exert its biological functions by mediating multiple signaling pathways in neurological diseases, such as Alzheimer's disease (AD), cognitive dysfunction, ischemic stroke, post-stroke depression, cerebral small-vessel disease, hypoxic-ischemic encephalopathy, traumatic brain injury, spinal cord injury, Parkinson's disease (PD), epilepsy, neuropathic pain, and autoimmune diseases. In these diseases, PKM2 can exert various biological functions, including regulation of glycolysis, inflammatory responses, apoptosis, proliferation of cells, oxidative stress, mitochondrial dysfunction, or pathological autoimmune responses. Moreover, the complexity of PKM2's biological characteristics determines the diversity of its biological functions. However, the role of PKM2 is not entirely the same in different diseases or cells, which is related to its oligomerization, subcellular localization, and post-translational modifications. This article will focus on the biological characteristics of PKM2, the regulation of PKM2 expression, and the biological role of PKM2 in neurological diseases. With this review, we hope to have a better understanding of the molecular mechanisms of PKM2, which may help researchers develop therapeutic strategies in clinic.
丙酮酸激酶 M2（PKM2）是糖酵解中的关键限速酶。众所周知，PKM2 在肿瘤细胞的增殖中起着至关重要的作用。然而，PKM2 还可以通过介导神经退行性疾病中的多种信号通路发挥其生物学功能，如阿尔茨海默病（AD）、认知功能障碍、缺血性中风、中风后抑郁、脑小血管病、缺氧缺血性脑病、创伤性脑损伤、脊髓损伤、帕金森病（PD）、癫痫、神经病理性疼痛和自身免疫性疾病。在这些疾病中，PKM2 可以发挥各种生物学功能，包括调节糖酵解、炎症反应、细胞凋亡、细胞增殖、氧化应激、线粒体功能障碍或病理性自身免疫反应。此外，PKM2 的生物学特性的复杂性决定了其生物学功能的多样性。然而，PKM2 的作用在不同的疾病或细胞中并不完全相同，这与其寡聚化、亚细胞定位和翻译后修饰有关。本文将重点介绍 PKM2 的生物学特性、PKM2 表达的调节以及 PKM2 在神经退行性疾病中的生物学作用。通过这篇综述，我们希望对 PKM2 的分子机制有更好的理解，这可能有助于研究人员在临床上开发治疗策略。
