Balancing Apoptosis and Autophagy for Parkinson's Disease Therapy: Targeting BCL-2

Apoptosis and autophagy are important intracellular processes that maintain organism homeostasis and promote survival. Autophagy selectively degrades damaged cellular organelles and protein aggregates, while apoptosis removes damaged or aged cells. Maintaining a balance between autophagy and apoptosis is critical for cell fate, especially for long-lived cells such as neurons. Conversely, their imbalance is associated with neurodegenerative diseases such as Parkinson's disease (PD), which is characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Restoring the balance between autophagy and apoptosis is a promising strategy for the treatment of PD. Some core proteins engage in cross talk between apoptosis and autophagy, including B cell lymphoma (BCL)-2 family members. This Review summarizes the role of BCL-2 members in the regulation of apoptosis and autophagy and discusses potential therapeutic approaches that target this balance for PD treatment.