Spermine oxidase: A promising therapeutic target for neurodegeneration in diabetic retinopathy.
Diabetic retinopathy
Neurodegeneration
Neuroprotection
Oxidative stress
Polyamine metabolism
Spermine oxidase
Journal
Pharmacological research
ISSN: 1096-1186
Titre abrégé: Pharmacol Res
Pays: Netherlands
ID NLM: 8907422
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
31
12
2018
revised:
23
04
2019
accepted:
05
06
2019
pubmed:
18
6
2019
medline:
22
7
2020
entrez:
18
6
2019
Statut:
ppublish
Résumé
Diabetic Retinopathy (DR), is a significant public health issue and the leading cause of blindness in working-aged adults worldwide. The vision loss associated with DR affects patients' quality of life and has negative social and psychological effects. In the past, diabetic retinopathy was considered as a vascular disease; however, it is now recognized to be a neuro-vascular disease of the retina. Current therapies for DR, such as laser photocoagulation and anti-VEGF therapy, treat advanced stages of the disease, particularly the vasculopathy and have adverse side effects. Unavailability of effective treatments to prevent the incidence or progression of DR is a major clinical problem. There is a great need for therapeutic interventions capable of preventing retinal damage in DR patients. A growing body of evidence shows that neurodegeneration is an early event in DR pathogenesis. Therefore, studies of the underlying mechanisms that lead to neurodegeneration are essential for identifying new therapeutic targets in the early stages of DR. Deregulation of the polyamine metabolism is implicated in various neurodegenerative diseases, cancer, renal failure, and diabetes. Spermine Oxidase (SMOX) is a highly inducible enzyme, and its dysregulation can alter polyamine homeostasis. The oxidative products of polyamine metabolism are capable of inducing cell damage and death. The current review provides insight into the SMOX-regulated molecular mechanisms of cellular damage and dysfunction, and its potential as a therapeutic target for diabetic retinopathy. Structural and functional changes in the diabetic retina and the mechanisms leading to neuronal damage (excitotoxicity, loss of neurotrophic factors, oxidative stress, mitochondrial dysfunction etc.) are also summarized in this review. Furthermore, existing therapies and new approaches to neuroprotection are discussed.
Identifiants
pubmed: 31207342
pii: S1043-6618(18)32027-9
doi: 10.1016/j.phrs.2019.104299
pmc: PMC7011157
mid: NIHMS1537839
pii:
doi:
Substances chimiques
Polyamines
0
Oxidoreductases Acting on CH-NH Group Donors
EC 1.5.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
104299Subventions
Organisme : NEI NIH HHS
ID : R01 EY028569
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
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