The article discusses the progression of Parkinson's disease (PD) and the neurobiology of axon degeneration. Despite advances in understanding the molecular basis of PD, effective therapies to halt disease progression remain elusive. The authors argue that axon degeneration, rather than cell body death, is the primary driver of clinical progression in PD. They propose that axon degeneration is a distinct process from the canonical pathways of programmed cell death (PCD) and should be a focus for future therapeutic strategies. The study highlights that axon degeneration occurs early in PD and is not adequately addressed in current theories of disease pathogenesis. Evidence from genetic studies, such as those involving α-synuclein and LRRK2 mutations, supports the idea that axon dysfunction is an early feature of PD. Additionally, the WldS mouse model demonstrates that axons can survive even when the neuronal soma is destroyed, suggesting that axon protection could be a viable therapeutic target. The article also discusses the molecular mechanisms of axon and cell body degeneration, noting that they are distinct processes. While caspases are involved in cell body death, they do not play a significant role in axon degeneration. This distinction has important implications for the development of neuroprotective strategies in PD. The study emphasizes the need for a new focus on axon degeneration in the search for effective therapies for PD. It suggests that protecting axons, rather than cell bodies, could be a more promising approach. The authors also highlight the importance of understanding the neurobiology of axons in the context of neurorestorative approaches to PD treatment. Overall, the article calls for a re-evaluation of current therapeutic strategies in light of the growing evidence that axon degeneration is a key factor in the progression of PD.The article discusses the progression of Parkinson's disease (PD) and the neurobiology of axon degeneration. Despite advances in understanding the molecular basis of PD, effective therapies to halt disease progression remain elusive. The authors argue that axon degeneration, rather than cell body death, is the primary driver of clinical progression in PD. They propose that axon degeneration is a distinct process from the canonical pathways of programmed cell death (PCD) and should be a focus for future therapeutic strategies. The study highlights that axon degeneration occurs early in PD and is not adequately addressed in current theories of disease pathogenesis. Evidence from genetic studies, such as those involving α-synuclein and LRRK2 mutations, supports the idea that axon dysfunction is an early feature of PD. Additionally, the WldS mouse model demonstrates that axons can survive even when the neuronal soma is destroyed, suggesting that axon protection could be a viable therapeutic target. The article also discusses the molecular mechanisms of axon and cell body degeneration, noting that they are distinct processes. While caspases are involved in cell body death, they do not play a significant role in axon degeneration. This distinction has important implications for the development of neuroprotective strategies in PD. The study emphasizes the need for a new focus on axon degeneration in the search for effective therapies for PD. It suggests that protecting axons, rather than cell bodies, could be a more promising approach. The authors also highlight the importance of understanding the neurobiology of axons in the context of neurorestorative approaches to PD treatment. Overall, the article calls for a re-evaluation of current therapeutic strategies in light of the growing evidence that axon degeneration is a key factor in the progression of PD.