Chronic ISR Activation Represses Axonal Protein Synthesis in Nigrostriatal Dopaminergic Neurons in Parkinson's Disease

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In ALS motor neurons, chronic ISR activation via eIF2α phosphorylation creates a pathological state that represses axonal protein synthesis below the threshold needed for synaptic maintenance. Analogously, in Parkinson's disease, α-synuclein aggregation, mitochondrial dysfunction, and ER stress may chronically activate PERK/GCN2/PKR, driving eIF2α~P that suppresses axonal translation in nigrostria