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

4 hours ago

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.

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