Metabolism of Polyamines and Kidney Disease: A Promising Therapeutic Target

Abstract

Background: More than 850 million people worldwide suffer from acute and chronic kidney diseases (CKD) which are tremendous socioeconomic burdens for society. Currently, the treatment choices for CKD are limited. There is a great need to understand the underlying mechanisms of the development of CKD in order to develop potential therapeutic strategies. Summary: The alteration in cellular metabolism has emerged as an important common pathological mechanism in different kidney diseases. Metabolic intervening and reprogramming will yield new insights to prevent and slow the progression of kidney disease. As one essential component of cellular metabolisms in fuel-source preferences (glucose, fatty acids, or ketones), the polyamine compound metabolism comprising the metabolites (spermine, spermidine, and putrescine) and their biosynthetic and catabolic enzymes are an endogenous pathophysiological regulator that is arising as a potential therapeutic object for many diseases. Key Messages: This article aims to review current knowledge on polyamine metabolism and physiological processes, and its potential regulatory and beneficial roles in immunoregulation, mitochondrial homeostasis, autophagy, DNA damage, and kidney diseases, and thus provide a novel therapeutic opportunity for kidney diseases.

The causal role between circulating immune cells and diabetic nephropathy: a bidirectional Mendelian randomization with mediating insights

“…Polyamines are essential biomolecules widely present in cellular metabolism. High glucose levels may cause abnormal polyamine metabolism in rat kidney tissues, inducing podocyte apoptosis and reduced autophagy, which could be a crucial mechanism in DN [ 43 ]. The content of polyamines and the glycolytic supply play a pivotal role in the immune activity of NK cells [ 44 ].…”

Recommendations for nutritional supplements for dry eye disease: current advances

“…Spermidine is a naturally occurring polyamine found in all living organisms, playing essential roles in cellular metabolism ( Hofer et al, 2021 ), including cell proliferation and division ( Luo et al, 2023 ). It is critical for maintaining DNA stability and synthesis ( Wang et al, 2018 ) and supports processes such as apoptosis and autophagy, crucial for removing damaged cells and maintaining cellular health ( Hofer et al, 2021 ).…”

Structural Insights into the Mechanisms Underlying Polyaminopathies

“…For a long time, whether and how polyamine homeostasis directly causes diseases has been controversial. Excessive depletion or accumulation of polyamines can negatively affect cells in aging [ 7 ], renal failure [ 8 ], neurodegenerative disease [ 9 ], and cancer [ 10 ]. Elevated levels of polyamines can promote the proliferation of cancer cells and tumor growth, while decreased levels of polyamines may lead to cell growth arrest.…”