The influence of BACE1 on macrophage recruitment and activity in the injured peripheral nerve.
The influence of BACE1 on macrophage recruitment and activity in the injured peripheral nerve.
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DOI：
10.1186/s12974-021-02121-2
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发表时间：
2021-03-15
影响因子：
9.3
通讯作者：
Farah MH
中科院分区：
文献类型：
--
作者：
Fissel JA;Farah MH
周围神经损伤后，包括轴突、雪旺细胞和巨噬细胞在内的多种细胞类型协同促进神经再生。然而，这种修复能力是有限的，特别是在老年人中，目前的治疗方法是不够的。再生反应的一个关键组成部分是受损神经微环境中的细胞间信号网络。Sheddases在周围神经中表达，并通过跨膜蛋白的裂解调控细胞间信号传导，从而通过顺式和跨细胞调控机制调控多种通路。在脱落酶β -分泌酶（BACE1）缺失的小鼠中观察到轴突再生增强，BACE1是一种跨膜天冬氨酸蛋白酶，已在阿尔茨海默病的背景下进行了研究。BACE1敲除（KO）小鼠在神经损伤后显示出增强的巨噬细胞募集和活性，尽管尚不清楚这是否在驱动增强的轴突再生中起作用。此外，BACE1增加巨噬细胞募集和活性的机制尚不清楚。BACE1有许多底物，其中一些已知具有免疫调节活性。本文将讨论BACE1和其他酶在周围神经再生中的作用，概述已知的免疫调节BACE1底物及其在周围神经再生中的潜在作用。目前的文献表明，在这一过程中，由神经元和雪旺细胞表达的BACE1和底物可能比巨噬细胞表达的BACE1和底物更重要。更广泛地说，BACE1可能作为外周神经以外的免疫调节效应物发挥作用。
Following peripheral nerve injury, multiple cell types, including axons, Schwann cells, and macrophages, coordinate to promote nerve regeneration. However, this capacity for repair is limited, particularly in older populations, and current treatments are insufficient. A critical component of the regeneration response is the network of cell-to-cell signaling in the injured nerve microenvironment. Sheddases are expressed in the peripheral nerve and play a role in the regulation if this cell-to-cell signaling through cleavage of transmembrane proteins, enabling the regulation of multiple pathways through cis- and trans-cellular regulatory mechanisms. Enhanced axonal regeneration has been observed in mice with deletion of the sheddase beta-secretase (BACE1), a transmembrane aspartyl protease that has been studied in the context of Alzheimer’s disease. BACE1 knockout (KO) mice display enhanced macrophage recruitment and activity following nerve injury, although it is unclear whether this plays a role in driving the enhanced axonal regeneration. Further, it is unknown by what mechanism(s) BACE1 increases macrophage recruitment and activity. BACE1 has many substrates, several of which are known to have immunomodulatory activity. This review will discuss current knowledge of the role of BACE1 and other sheddases in peripheral nerve regeneration and outline known immunomodulatory BACE1 substrates and what potential roles they could play in peripheral nerve regeneration. Currently, the literature suggests that BACE1 and substrates that are expressed by neurons and Schwann cells are likely to be more important for this process than those expressed by macrophages. More broadly, BACE1 may play a role as an effector of immunomodulation beyond the peripheral nerve.
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影响因子：
11.1
作者：
Bolino A;Piguet F;Alberizzi V;Pellegatta M;Rivellini C;Guerrero-Valero M;Noseda R;Brombin C;Nonis A;D'Adamo P;Taveggia C;Previtali SC
通讯作者：
Previtali SC
影响因子：
16.6
作者：
Gama-Norton L;Ferrando E;Ruiz-Herguido C;Liu Z;Guiu J;Islam AB;Lee SU;Yan M;Guidos CJ;López-Bigas N;Maeda T;Espinosa L;Kopan R;Bigas A
通讯作者：
Bigas A
影响因子：
12.4
作者：
通讯作者：
--
影响因子：
4.4
作者：
BRUCK, W;FRIEDE, RL
通讯作者：
FRIEDE, RL
DOI：
10.1073/pnas.95.17.9985
发表时间：
1998-08-18
影响因子：
11.1
作者：
Coleman, MP;Conforti, L;Perry, VH
通讯作者：
Perry, VH