Gupta Shiwangi, Kishore Abhinoy, Rishi Vikas, Aggarwal Aanchal
National Agri-Food Biotechnology Institute, SAS Nagar, Knowledge City, Sector-81, Mohali, Punjab, 140306, India.
Department of Biotechnology, Panjab University, Sector-25, BMS Block I, Chandigarh, India.
Mol Neurobiol. 2025 Jun 3. doi: 10.1007/s12035-025-05045-7.
Spines, the anatomical specializations on nerve cells, undergo persistent remodeling that often drives synapse development and plasticity. This remodeling is primarily driven by cytoskeletal regulation and local protein synthesis, both of which shape spine morphology. The cytoskeleton, composed mainly of actin filaments and microtubules, provides structural integrity and plasticity to spines by tuning their dynamics. Complementing this, local protein synthesis supports spine growth and modification by enabling localized trafficking and translation of synaptic mRNAs. At a given time, stimuli elicit a cascade of synaptic events involving both cytoskeletal dynamics and localized translation that converge to orchestrate spine development. Importantly, these events are not governed solely by immediate cellular signaling; rather, it extends to include epigenetic modifiers that exert control over the spatial and temporal dynamics of spine development. Aberrant expression of such modifiers can disrupt spine development and contribute to synaptopathies-neurological disorders rooted from synaptic dysfunction. Previous research has cursorily examined how epigenetic regulation contributes to neurodegenerative diseases, lacking detailed exploration of epigenetics in individual synaptic events. However, understanding spine reprogramming and its epigenetic, underpinnings need to be deciphered. Emerging evidence suggests altered epigenetic profiles disturb the coordinated balance of synaptic machinery and its structural architecture. Here, we review the stochastic mechanisms influencing spine and synapse morphology, emphasizing cytoskeletal maintenance and local protein synthesis-and how these events are tuned in light of epigenetic regulation.
树突棘是神经细胞上的解剖学特化结构，会经历持续的重塑，这种重塑常常驱动突触的发育和可塑性。这种重塑主要由细胞骨架调节和局部蛋白质合成驱动，二者共同塑造树突棘的形态。细胞骨架主要由肌动蛋白丝和微管组成，通过调节其动力学为树突棘提供结构完整性和可塑性。与之相辅相成的是，局部蛋白质合成通过实现突触mRNA的局部运输和翻译来支持树突棘的生长和修饰。在特定时刻，刺激会引发一系列突触事件，这些事件涉及细胞骨架动力学和局部翻译，二者共同协调树突棘的发育。重要的是，这些事件并非仅由即时细胞信号控制；相反，它还包括表观遗传修饰因子，这些因子对树突棘发育的时空动力学发挥控制作用。此类修饰因子的异常表达会破坏树突棘发育，并导致突触病——即源于突触功能障碍的神经疾病。先前的研究已粗略探讨了表观遗传调控如何导致神经退行性疾病，但缺乏对单个突触事件中表观遗传学的详细研究。然而，需要解读树突棘重编程及其表观遗传学基础。新出现的证据表明，表观遗传谱的改变会扰乱突触机制及其结构架构的协调平衡。在这里，我们回顾影响树突棘和突触形态的随机机制，重点关注细胞骨架维持和局部蛋白质合成，以及这些事件如何根据表观遗传调控进行调节。
