近日，日本东京大学Noboru Mizushima及其团队的最新研究揭示了小鼠自噬的可逆抑制揭示了神经元的恢复能力。相关论文发表在2026年6月25日出版的《科学》杂志上。

研究组开发了一个小鼠模型，其中自噬可以快速可逆地调节，以研究这些缺陷的可逆性。抑制自噬导致蛋白质组和转录组的改变、内含体的积累和轴突的肿胀，这些在自噬恢复后都得到了很大的改善。与这些细胞异常一致，自噬抑制诱导运动和认知功能障碍，自噬恢复也逆转。他们的发现阐明了细胞内清除所带来的神经元功能和质量的潜在弹性。

据悉，细胞内质量控制机制的损伤，包括自噬，影响神经元的完整性和功能。尽管许多研究旨在减缓神经元的退化，但尚不清楚神经元功能和细胞内质量一旦受损是否可以恢复。

附：英文原文

Title: Reversible suppression of autophagy in a mouse model reveals neuronal resilience

Author: Tomoya Eguchi, Manabu Abe, Takuya Tomita, Hideaki Morishita, Yasushi Saeki, Kenji Sakimura, Kenji F. Tanaka, Noboru Mizushima

Issue&Volume: 2026-06-25

Abstract: Impairments in intracellular quality-control mechanisms, including autophagy, affect neuronal integrity and function. Despite numerous studies aimed at slowing neuronal deterioration, it remains unclear whether neuronal function and intracellular quality can be restored once impaired. We developed a mouse model in which autophagy could be rapidly and reversibly regulated to investigate the reversibility of such defects. Suppressing autophagy led to proteome and transcriptome changes, inclusion body accumulation, and axonal swelling, all of which were largely ameliorated after autophagy restoration. Consistent with these cellular abnormalities, autophagy suppression induced motor and cognitive dysfunction, which was also reversed on autophagy restoration. Our findings elucidate the potential resilience of neuronal function and quality enabled by intracellular clearance.

DOI: ady3911

Source: https://www.science.org/doi/10.1126/science.ady3911