Neurodegenerative diseases are characterized by the formation and propagation of protein aggregates, especially amyloid fibrils. However, what normally suppresses protein misfolding and aggregation in metazoan cells remains incompletely understood. Here, we show that TRIM11, a member of the metazoan tripartite motif (TRIM) family, both prevents the formation of protein aggregates and dissolves pre-existing protein deposits, including amyloid fibrils. These molecular chaperone and disaggregase activities are ATP independent. They enhance folding and solubility of normal proteins and cooperate with TRIM11 SUMO ligase activity to degrade aberrant proteins. TRIM11 abrogates α-synuclein fibrillization and restores viability in cell models of Parkinson’s disease (PD). Intracranial adeno-associated viral delivery of TRIM11 mitigates α-synuclein-mediated pathology, neurodegeneration, and motor impairments in a PD mouse model. Other TRIMs can also function as ATP-independent molecular chaperones and disaggregases. Thus, we define TRIMs as a potent and multifunctional protein quality-control system in metazoa, which might be applied to treat neurodegenerative diseases.

神经退行性疾病的特征是蛋白质聚集体，尤其是淀粉样原纤维的形成和传播。然而，通常抑制后生动物细胞中蛋白质错误折叠和聚集的因素仍不完全清楚。在这里，我们证明 TRIM11 是后生动物三部分基序 (TRIM) 家族的成员，既可以防止蛋白质聚集体的形成，又可以溶解预先存在的蛋白质沉积物，包括淀粉样蛋白原纤维。这些分子伴侣和解聚酶活性与 ATP 无关。它们增强正常蛋白质的折叠和溶解度，并与 TRIM11 SUMO 连接酶活性配合降解异常蛋白质。 TRIM11 可消除帕金森病 (PD) 细胞模型中的 α-突触核蛋白纤维化并恢复活力。 TRIM11 的颅内腺相关病毒递送可减轻 PD 小鼠模型中 α-突触核蛋白介导的病理、神经变性和运动障碍。其他 TRIM 也可以充当不依赖于 ATP 的分子伴侣和解聚酶。因此，我们将 TRIM 定义为后生动物中一种有效的多功能蛋白质质量控​​制系统，可用于治疗神经退行性疾病。