Secretory autophagy: a turn key for understanding AMD pathology and developing new therapeutic targets?
Expert Opin Ther Targets
; 26(10): 883-895, 2022 10.
Article
em En
| MEDLINE
| ID: mdl-36529978
ABSTRACT
INTRODUCTION:
Age-related macular degeneration (AMD) is an eye disease leading to vision loss with poorly known pathogenesis and limited therapeutic options. Degradative autophagy (DA) is impaired in AMD, but emerging evidence points to secretary autophagy (SA) as a key element in AMD pathogenesis. AREAS COVERED SA may cause the release of proteins and protein aggregates, lipofuscin, beta amyloid, faulty mitochondria, pro-inflammatory and pro-angiogenic factors from the retinal pigment epithelium (RPE) that may contribute to drusen formation and choroidal neovascularization. SA may replace DA, when formation of autolysosome is impaired, and then a harmful cargo, instead of being degraded, is extruded from the RPE contributing to drusen and/or angiogenic environment. Therefore, the interplay between DA and SA may be critical for drusen formation and choroidal neovascularization, so it can be a turn key to understand AMD pathogenesis. EXPERT OPINION Although SA fulfills some beneficial functions, it is detrimental for the retina in many cases. Therefore, inhibiting SA may be a therapeutic strategy in AMD, but it is challenged by the development of selective SA inhibitors that would not affect DA. The TRIM16, SEC22B and RAB8A proteins, specific for secretory autophagosome, may be primary candidates as therapeutic targets, but their action is not limited to autophagy and therefore requires further studies.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neovascularização de Coroide
/
Degeneração Macular
Limite:
Humans
Idioma:
En
Revista:
Expert Opin Ther Targets
Ano de publicação:
2022
Tipo de documento:
Article