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Role of A-Kinase Anchoring Protein 1 in Retinal Ganglion Cells: Neurodegeneration and Neuroprotection
Journal article   Open access   Peer reviewed

Role of A-Kinase Anchoring Protein 1 in Retinal Ganglion Cells: Neurodegeneration and Neuroprotection

Tonking Bastola, Guy Perkins, Kim Keun-Young, Seunghwan Choi, Kwon Jin-Woo, Ziyao Shen, Stefan Strack and Won-Kyu Ju
Cells (Basel, Switzerland), Vol.12(11), 1539
01/01/2023
DOI: 10.3390/cells12111539
PMCID: PMC10252895
PMID: 37296658
url
https://doi.org/10.3390/cells12111539View
Published (Version of record) Open Access

Abstract

A-Kinase anchoring protein 1 (AKAP1) is a multifunctional mitochondrial scaffold protein that regulates mitochondrial dynamics, bioenergetics, and calcium homeostasis by anchoring several proteins, including protein kinase A, to the outer mitochondrial membrane. Glaucoma is a complex, multifactorial disease characterized by a slow and progressive degeneration of the optic nerve and retinal ganglion cells (RGCs), ultimately resulting in vision loss. Impairment of the mitochondrial network and function is linked to glaucomatous neurodegeneration. Loss of AKAP1 induces dynamin-related protein 1 dephosphorylation-mediated mitochondrial fragmentation and loss of RGCs. Elevated intraocular pressure triggers a significant reduction in AKAP1 protein expression in the glaucomatous retina. Amplification of AKAP1 expression protects RGCs from oxidative stress. Hence, modulation of AKAP1 could be considered a potential therapeutic target for neuroprotective intervention in glaucoma and other mitochondria-associated optic neuropathies. This review covers the current research on the role of AKAP1 in the maintenance of mitochondrial dynamics, bioenergetics, and mitophagy in RGCs and provides a scientific basis to identify and develop new therapeutic strategies that could protect RGCs and their axons in glaucoma.
Bioenergetics Nervous System Oxidative Stress Phosphorylation Signal Transduction A kinase-anchoring protein Calcium (mitochondrial) Calcium homeostasis Calcium signalling Dephosphorylation Dynamin Glaucoma Homeostasis Kinases Localization Mitochondria Motility Neurodegeneration Neuropathy Neuroprotection Optic nerve Protein kinase A Proteins Retina Retinal ganglion cells Therapeutic targets

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