Nutrients, hormones and the energy sensor AMP-activated protein kinase (AMPK) tightly regulate the intracellular levels of the metabolic intermediary malonyl-CoA, which is a precursor of fatty acid synthesis and a negative regulator of fatty acid oxidation. In the brain, the involvement of malonyl-CoA in the control of food intake and energy homeostasis has been known for decades. However, recent data uncover a new role in cognition and brain development. The sensing of malonyl-CoA by carnitine palmitoyltransferase 1 (CPT1) proteins regulates a variety of functions, such as the fate of neuronal stem cell precursors, the motility of lysosomes in developing axons, the trafficking of glutamate receptors to the neuron surface (necessary for proper synaptic function) and the metabolic coupling between astrocytes and neurons. We discuss the relevance of those recent findings evidencing how nutrients and metabolic disorders impact cognition. We also enumerate all nutritional and hormonal conditions that are known to regulate malonyl-CoA levels in the brain, reflect on protein malonylation as a new post-translational modification, and give a reasoned vision of the opportunities and challenges that future research in the field could address.

营养素、激素和能量传感器 AMP 活化蛋白激酶 (AMPK) 严格调节代谢中间体丙二酰辅酶 A 的细胞内水平，丙二酰辅酶 A 是脂肪酸合成的前体和脂肪酸氧化的负调节剂。在大脑中，丙二酰辅酶A参与控制食物摄入和能量稳态已经有几十年了。然而，最近的数据揭示了认知和大脑发育中的新作用。肉碱棕榈酰转移酶 1 (CPT1) 蛋白对丙二酰辅酶 A 的感知调节多种功能，例如神经元干细胞前体的命运、溶酶体在轴突发育过程中的运动、谷氨酸受体运输到神经元表面（对于适当的突触功能）和星形胶质细胞和神经元之间的代谢耦合。我们讨论了那些证明营养和代谢紊乱如何影响认知的最新发现的相关性。我们还列举了所有已知可调节大脑中丙二酰辅酶A水平的营养和激素条件，将蛋白质丙二酰化作为一种​​新的翻译后修饰进行反思，并对该领域未来研究可能面临的机遇和挑战给出合理的看法地址。