Deciphering the Neuroautophagic Interactome: Molecular Circuits Linking Selective Autophagy to Neuropathological Cascades in Neurological Disorders.

Selective autophagy, a lysosome-dependent degradation pathway targeting specific substrates (e.g., mitochondria, protein aggregates), plays a pivotal role in maintaining neuronal homeostasis. Its dysregulation is intricately linked to neurodegenerative diseases, acute brain injuries, and neuroinflammatory disorders. This review elucidates the crosstalk between selective autophagy and key neuropathophysiological processes, including apoptosis, neuroinflammation, oxidative stress, and blood-brain barrier disruption. We delineate the dual roles of selective autophagy through the framework of the neuroautophagic interactome-a network in which kinases (ULK1, TBK1) and effectors (PINK1/Parkin, SQSTM1/p62) collaboratively interpret ubiquitin codes. This integrated signaling nexus functions as a decisive hub that bidirectionally modulates disease progression. Furthermore, we evaluate emerging therapeutic strategies targeting selective autophagy to mitigate neuronal damage, emphasizing its dual role as both a protector and a contributor to disease progression.