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MeSH: normotenzní glaukom-genetika

1 záznamů v PubMed Filtry

Článek

Optineurin-facilitated axonal mitochondria delivery promotes neuroprotection and axon regeneration

Liu, Dong
Autor Liu, Dong ORCID Spencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA, USA
Webber, Hannah C
Autor Webber, Hannah C Spencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA, USA
Bian, Fuyun
Autor Bian, Fuyun Spencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA, USA
Xu, Yangfan
Autor Xu, Yangfan Spencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA, USA Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences; Shanghai Research Center of Ophthalmology and Optometry, Shanghai, P.R. China
Prakash, Manjari
Autor Prakash, Manjari Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Prague West, Czechia
Feng, Xue
Autor Feng, Xue Spencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA, USA
Yang, Ming
Autor Yang, Ming Spencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA, USA
Yang, Hang
Autor Yang, Hang Spencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA, USA
You, In-Jee
Autor You, In-Jee ORCID Spencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA, USA
Li, Liang
Autor Li, Liang ORCID Spencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA, USA

Nature communications. 2025 Feb 20 ; 16 (1) : 1789. [epub] 20250220

Nat Commun
ISSN 2041-1723
Zdroj

Optineurin (OPTN) mutations are linked to amyotrophic lateral sclerosis (ALS) and normal tension glaucoma (NTG), but a relevant animal model is lacking, and the molecular mechanisms underlying neurodegeneration are unknown. We find that OPTN C-terminus truncation (OPTN∆C) causes late-onset neurodegeneration of retinal ganglion cells (RGCs), optic nerve (ON), and spinal cord motor neurons, preceded by a decrease of axonal mitochondria in mice. We discover that OPTN directly interacts with both microtubules and the mitochondrial transport complex TRAK1/KIF5B, stabilizing them for proper anterograde axonal mitochondrial transport, in a C-terminus dependent manner. Furthermore, overexpressing OPTN/TRAK1/KIF5B prevents not only OPTN truncation-induced, but also ocular hypertension-induced neurodegeneration, and promotes robust ON regeneration. Therefore, in addition to generating animal models for NTG and ALS, our results establish OPTN as a facilitator of the microtubule-dependent mitochondrial transport necessary for adequate axonal mitochondria delivery, and its loss as the likely molecular mechanism of neurodegeneration.

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