Lin Heng, Ramanan Sudarshan, Kaplan Sofia, King Darron H, Bunn Dominic, Johnson Gail V W
Department of Anesthesiology and Perioperative Medicine, University of Rochester, Rochester, New York.
Department of Anesthesiology and Perioperative Medicine, University of Rochester, Rochester, New York.
Biol Psychiatry. 2025 Jan 8. doi: 10.1016/j.biopsych.2024.12.019.
There is an increasing awareness that B-cell lymphoma 2 (Bcl-2)-associated athanogene (BAG) proteins play critical roles in maintaining neural homeostasis and that their dysregulation contributes to neurological disorders. This protein family, which comprises 9 members, is evolutionarily conserved, with each member having at least one BAG domain that binds to the nucleotide-binding domains of Hsp70 family members. Collectively, these proteins are essential for the proper functioning of the central nervous system (CNS). Although numerous studies have focused on a specific BAG protein, an understanding of how BAG family members may act cooperatively to maintain cellular homeostasis is needed. In this review, we give an overview of the BAG domain interactors Hsp72, Hsp70.2, CHIP, and METTL3, which are common to all BAG family members. This is followed by a concise description of each BAG family member, with a focus on its function in the CNS and dysfunction in neurological conditions. Finally, we discuss the intersection of the molecular functions of the different BAG family proteins by delineating similarities and differences and describing how their functions can be either complementary or competing. The information in this review provides a basic conceptual framework for analyzing the roles of a particular BAG family member in the CNS and neurological conditions. This review also provides a basis for examining how BAG family members can play either redundant or antagonistic roles that may modulate experimental outcomes.
人们越来越意识到，B细胞淋巴瘤2（Bcl-2）相关抗凋亡基因（BAG）蛋白在维持神经稳态中起关键作用，其失调会导致神经疾病。这个由9个成员组成的蛋白家族在进化上是保守的，每个成员至少有一个与热休克蛋白70（Hsp70）家族成员的核苷酸结合结构域结合的BAG结构域。总体而言，这些蛋白对中枢神经系统（CNS）的正常功能至关重要。尽管众多研究聚焦于特定的BAG蛋白，但仍需要了解BAG家族成员如何协同作用以维持细胞稳态。在本综述中，我们概述了所有BAG家族成员共有的BAG结构域相互作用蛋白Hsp72、Hsp70.2、CHIP和METTL3。随后简要描述每个BAG家族成员，重点关注其在中枢神经系统中的功能以及在神经疾病中的功能障碍。最后，我们通过阐述异同点并描述它们的功能如何互补或相互竞争，来讨论不同BAG家族蛋白分子功能的交叉点。本综述中的信息为分析特定BAG家族成员在中枢神经系统和神经疾病中的作用提供了一个基本概念框架。本综述还为研究BAG家族成员如何发挥冗余或拮抗作用以调节实验结果提供了基础。
