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

Abstract

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 in PD pathogenesis, such as α-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. Expected final online publication date for the Annual Review of Biochemistry, Volume 92 is June 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Polyamines in Edible and Medicinal Fungi from Serbia: A Novel Perspective on Neuroprotective Properties

“…Interestingly, G. applanatum, which exhibited significant AChE inhibition, also demonstrated a higher concentration of PUT and SPD compared to G. resinaceum. The presence of the elevated levels PUT and SPD in G. applanatum may also contribute to its pronounced AChE inhibitory effects, since these PAs have been implicated in neuroprotective mechanisms and may interact with AChE, potentially altering its catalytic activity due to its positive charge and chaperone-like activity [15,69]. This is supported by the results of the correlation analysis, which showed a high positive correlation between AChE inhibition and levels of PUT and SPD (Figure 3).…”

“…Polyamines (PAs) represent a ubiquitous category of small, positively charged polycations within the broader spectrum of biogenic amines [13,14]. They play a crucial role in various physiological processes, including but not limited to cell growth, gene regulation, autophagy, differentiation, proliferation, the modulation of ion channels, the regulation of inflammation, oxidative stress management, and immune responses [1,13,15]. Triamine spermidine (SPD), tetraamine spermine (SPM), and diamine precursor putrescine (PUT) are the most common natural amines found extensively in all cells, but variations in PA concentrations have been observed in fruits, vegetables, and animal-derived food products [2].…”

“…Examples of food and beverages rich in PAs include rice bran, green pepper, broccoli, soybeans, mushrooms, oranges, and green tea, which opens avenues for exploring the potential correlation between PA intake and the aging process, providing a practical approach to studying their effects on longevity and antioxidant activity as well [1,[15][16][17]. Studies have demonstrated that SPM, SPD, and PUT effectively act as free radical scavengers, bind to toxic aldehydes, and showcase chelating abilities toward metal ions, while SPM and SPD exhibit the capacity to modify the activity of antioxidant enzymes through their chaperone-like activity and through the alternation of gene expression, contributing to the modulation of oxidative stress-triggering mechanisms [1,11,18,19].…”

Bioactive components and mechanisms of Pu-erh tea in improving levodopa metabolism in rats through COMT inhibition

“…3–5 PD is the second most common neurodegenerative disease after AD and affects many middle-aged and elderly people around the world. 6 The main characteristic of PD is a decrease in DA secretion in the brain due to the degeneration of nigrostriatal dopaminergic neurons. 7 Levodopa ( l -DOPA) remains the most effective drug for PD.…”

Potential therapeutic role of spermine via Rac1 in osteoporosis: Insights from zebrafish and mice

“…Spermine (SPM), an in vivo synthesized polyamine derived from putrescine and S-adenosyl-L-methionine, originates from intestinal microorganisms, endogenous cellular processes, and dietary sources ( Sagar et al, 2021 ). SPM exhibits a broad spectrum of biological effects on cell proliferation ( Xu et al, 2023 ), oxidative stress ( Vrijsen et al, 2020 ), tumor growth ( Li et al, 2023b ), autophagy ( Vrijsen et al, 2023 ), and inflammation ( Cao et al, 2017 ; Jiang et al, 2021a ). Notably, a decline in blood SPM levels has been observed in individuals aged between 60 and 80 years, whereas centenarians maintain higher levels ( Pucciarelli et al, 2012 ).…”