Baudry Michel, Bi Xiaoning
Department of Basic Medical Sciences, College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766, USA.
Department of Biomedical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA.
Cells. 2025 Aug 22;14(17):1301. doi: 10.3390/cells14171301.
Although the calcium-dependent proteases, calpains, were discovered more than 60 years ago, we still know very little regarding their functions, mostly because very few studies are addressing questions related to specific members of this relatively large family of cysteine proteases. The "classical calpains", calpain-1 and calpain-2, are ubiquitous and have received more attention because of the special roles they play in the brain. The authors have been studying the properties and functions of these two calpain isoforms in the brain for over 45 years, and this review will focus on what has been learned over this period of time. In particular, we will discuss the numerous studies that have led to the notion that calpain-1 and calpain-2 play opposite functions in the brain on processes ranging from neuronal survival or death, synaptic plasticity, and learning and memory to neurogenesis. Mechanisms underlying these opposite functions are starting to be understood and the findings support the notion that such opposite functions might be a general feature of these two isoforms in any type of cell. This review concludes with a discussion of the potential benefits of selective calpain-2 inhibitors for the treatment of a variety of neurological disorders.
尽管钙依赖性蛋白酶——钙蛋白酶在60多年前就已被发现，但我们对其功能仍知之甚少，主要原因是很少有研究探讨这个相对较大的半胱氨酸蛋白酶家族中特定成员的相关问题。“经典钙蛋白酶”，即钙蛋白酶-1和钙蛋白酶-2，广泛存在且因其在大脑中发挥的特殊作用而受到更多关注。作者在大脑中研究这两种钙蛋白酶同工型的性质和功能已有45年多，本综述将聚焦这段时间内所了解到的情况。特别是，我们将讨论众多研究，这些研究得出了这样的观点：钙蛋白酶-1和钙蛋白酶-2在大脑中对从神经元存活或死亡、突触可塑性、学习和记忆到神经发生等一系列过程发挥着相反的作用。这些相反功能背后的机制正开始被理解，研究结果支持这样一种观点，即这种相反功能可能是这两种同工型在任何类型细胞中的一个普遍特征。本综述最后讨论了选择性钙蛋白酶-2抑制剂对治疗多种神经系统疾病的潜在益处。
