Polyamines in Parkinson's Disease: Balancing Between Neurotoxicity and Neuroprotection

The polyamines putrescine, spermidine, and spermine are abundant polycations of vital importance in mammalian cells. Their cellular levels are tightly regulated by degradation and synthesis, as well as by uptake and export. Here, we discuss the delicate balance between the neuroprotective and neurotoxic effects of polyamines in the context of Parkinson's disease (PD). Polyamine levels decline with aging and are altered in patients with PD, whereas recent mechanistic studies on ATP13A2 (PARK9) demonstrated a driving role of a disturbed polyamine homeostasis in PD. Polyamines affect pathways inPDpathogenesis, such as alpha-synuclein aggregation, and influence PD-related processes like autophagy, heavy metal toxicity, oxidative stress, neuroinflammation, and lysosomal/mitochondrial dysfunction. We formulate outstanding research questions regarding the role of polyamines in PD, their potential as PD biomarkers, and possible therapeutic strategies for PD targeting polyamine homeostasis.

Automated summary

The polyamines putrescine, spermidine, and spermine play a vital role in mammalian cells and are tightly regulated by various mechanisms. This article discusses the balance between the neuroprotective and neurotoxic effects of polyamines in Parkinson's disease (PD). Polyamine levels decline with aging and are altered in PD patients, and recent studies suggest a disrupted polyamine homeostasis as a driving factor in PD. Polyamines influence PD pathogenesis, such as alpha-synuclein aggregation, and affect PD-related processes like autophagy, heavy metal toxicity, oxidative stress, neuroinflammation, and lysosomal/mitochondrial dysfunction. The article also highlights outstanding research questions regarding the role of polyamines in PD, their potential as biomarkers, and possible therapeutic strategies targeting polyamine homeostasis.