Dopaminergic transmissive dormancy as a protective state against cellular stress

No therapies ensure long-term survival of dopaminergic neurons in Parkinson's disease. In this context, we propose that early neurodegeneration is an adaptive state of transmissive dormancy, not dysfunction. Upon sensing cellular stress, an inducible transcriptional program restricts cytosolic dopamine and actively silences neurotransmission. This adaptive response precedes neuronal death, reframing early symptoms as programmed dormancy rather than frank degeneration. Thus, reactivation strategies represent a compelling new approach to perhaps revive neural networks and abrogate disease. This principle may extend beyond the dopaminergic system and offers a new perspective on neurodegeneration.