Liu Yueqi, Li Hao, Liu Xuan, Wang Bin, Yang Hao, Wan Bo, Sun Miao, Xu Xingshun
Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Institute of Neuroscience, Soochow University, Suzhou, China.
Front Aging Neurosci. 2022 Sep 13;14:934725. doi: 10.3389/fnagi.2022.934725. eCollection 2022.
Due to the high clinical heterogeneity of neuronal intranuclear inclusion disease (NIID), it is easy to misdiagnose this condition and is considered to be a rare progressive neurodegenerative disease. More evidence demonstrates that NIID involves not only the central nervous system but also multiple systems of the body and shows a variety of symptoms, which makes a clinical diagnosis of NIID more difficult. This review summarizes the clinical symptoms in different systems and demonstrates that NIID is a multiple-system intranuclear inclusion disease. In addition, the core triad symptoms in the central nervous system, such as dementia, parkinsonism, and psychiatric symptoms, are proposed as an important clue for the clinical diagnosis of NIID. Recent studies have demonstrated that expanded GGC repeats in the 5'-untranslated region of the NOTCH2NLC gene are the cause of NIID. The genetic advances and possible underlying mechanisms of NIID (expanded GGC repeat-induced DNA damage, RNA toxicity, and polyglycine-NOTCH2NLC protein toxicity) are briefly summarized in this review. Interestingly, inflammatory cell infiltration and inflammation were observed in the affected tissues of patients with NIID. As a downstream pathological process of NIID, inflammation could be a therapeutic target for NIID.
由于神经元核内包涵体病（NIID）具有高度的临床异质性，该病容易被误诊，被认为是一种罕见的进行性神经退行性疾病。越来越多的证据表明，NIID不仅累及中枢神经系统，还涉及身体的多个系统，并表现出多种症状，这使得NIID的临床诊断更加困难。本综述总结了不同系统的临床症状，并表明NIID是一种多系统核内包涵体病。此外，还提出了中枢神经系统中的核心三联征症状，如痴呆、帕金森综合征和精神症状，作为NIID临床诊断的重要线索。最近的研究表明，NOTCH2NLC基因5'-非翻译区的GGC重复序列扩增是NIID的病因。本综述简要总结了NIID的遗传学进展和可能的潜在机制（GGC重复序列扩增诱导的DNA损伤、RNA毒性和聚甘氨酸-NOTCH2NLC蛋白毒性）。有趣的是，在NIID患者的受累组织中观察到炎症细胞浸润和炎症。作为NIID的下游病理过程，炎症可能是NIID的治疗靶点。
