Fundamental roles of the Optineurin gene in the molecular pathology of Amyotrophic Lateral Sclerosis

Shumin Zhao; Ranran Chen; Ying Gao; Yanchao Lu; Xue Bai; Jingjing Zhang

doi:10.3389/fnins.2023.1319706

Fundamental roles of the Optineurin gene in the molecular pathology of Amyotrophic Lateral Sclerosis

Front Neurosci. 2023 Dec 21:17:1319706. doi: 10.3389/fnins.2023.1319706. eCollection 2023.

Authors

Shumin Zhao^#^{1

2}, Ranran Chen^#^{1

2}, Ying Gao^{1

2}, Yanchao Lu^{1

2}, Xue Bai^{1

2}, Jingjing Zhang^{1

2}

Affiliations

¹ Department of Neurology, Medical Research Center, Chifeng Municipal Hospital, Chifeng, China.
² Chifeng Clinical Medical College of Inner Mongolia Medical University, Chifeng, China.

^# Contributed equally.

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons (MNs) in the brain and spinal cord. It is caused by multiple factors, including mutations in any one of several specific genes. Optineurin (OPTN) mutation is an essential cause of some familial and sporadic ALS. Besides, as a multifunctional protein, OPTN is highly expressed and conserved in the central nervous system. OPTN exerts its functions by interacting with various proteins, often acting as an adaptor to provide a link between two or more core proteins related to autophagy and inflammation, etc. OPTN mutation mainly results in its function deficiency, which alters these interactions, leading to functional impairment in many processes. Meanwhile, OPTN immunopositive inclusions are also confirmed in the cases of ALS due to C9ORF72, FUS, TARDBP, and SOD1 mutations. Therefore, OPTN gene may play fundamental roles in the molecular pathology of ALS in addition to OPTN mutation. In this review, we summarize the recent advances in the ALS pathology of OPTN defect, such as mitophagy disorder, neuroinflammation, neuronal axonal degeneration, vesicular transport dysfunction, etc., which will provide a reference for research on the pathogenesis and treatment of ALS.

Keywords: amyotrophic lateral sclerosis; mitophagy; neuroinflammation; optineurin; protein aggregation.

Publication types

Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The National Natural Science Foundation of China (82160320); The Central Government Guides Local Science and Technology Development Fund Projects (2021ZY0010); Inner Mongolia Medical University Science, and Technology Million Project Joint Project [YKD2018KJBW(LH)095].