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Autophagy-exosome crosstalk in neurodegeneration: Mechanisms and therapeutic opportunities - PubMed

4 hours ago
  • #exosomes
  • #autophagy
  • #neurodegeneration
  • Neurodegenerative diseases (NDs) share disrupted proteostasis due to impaired autophagy and maladaptive exosome dynamics.
  • Autophagy normally clears misfolded proteins, while exosomes facilitate neuroglial communication.
  • Impaired autophagy can redirect undegraded cargo into exosomes, spreading pathogenic proteins like amyloid-β and α-synuclein.
  • Dysregulation of autophagy-exosome crosstalk amplifies neuroinflammation, demyelination, and neuronal loss.
  • Pharmacological strategies include rapamycin and resveratrol to enhance autophagy, and engineered exosomes for neuroprotection.
  • Translational challenges include safety, biodistribution, dosing, and standardization.
  • AI and machine learning can aid in early diagnosis, patient stratification, and therapy optimization.
  • Deep learning may enable rational drug design for targeted exosome delivery to the brain.
  • The autophagy-exosome axis links intracellular clearance with intercellular signaling, offering diagnostic and therapeutic potential for NDs.