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Chaperone-mediated autophagy: the Achilles heel of the retinal pigment epithelium during age-related macular degeneration - PubMed

5 hours ago
  • #Chaperone-mediated autophagy
  • #Age-related macular degeneration
  • #Retinal pigment epithelium
  • Chaperone-mediated autophagy (CMA) is a selective autophagy pathway targeting proteins with a KFERQ-like motif for lysosomal degradation.
  • CMA decreases during physiological aging and its impairment is linked to age-related pathologies like cardiovascular disease and neurodegenerative disorders.
  • The study explores CMA's role in age-related macular degeneration (AMD), a leading cause of central vision loss.
  • The retinal pigment epithelium (RPE) shows early morphological and functional alterations in AMD, with CMA being selectively impaired in AMD patients.
  • Impaired CMA in AMD leads to accumulation of undegraded substrates, proteotoxicity, increased oxidative damage, and altered metabolism.
  • Using the CMA activator CA77.1, proteostasis was restored in AMD iPSC-RPE models, suggesting CMA as a novel druggable target for AMD.