Biophysica

Ion channels are fundamental membrane proteins that mediate selective ion flow across biological membranes and thereby govern excitability, signaling, and homeostasis in virtually all cell types. Although channel function is determined by intrinsic structural features, the surrounding lipid milieu is now recognized as a decisive regulatory layer. Lipids tune ion channel activity through complementary mechanisms: they can bind directly to channel proteins, reshape bilayer physical properties, or act as signaling messengers that couple extracellular cues to channel gating. In addition, the organization of membranes into lipid microdomains such as rafts and caveolae can cluster channels with receptors and scaffolds, enhancing signaling specificity and efficiency. Recent advances in cryo-electron microscopy and molecular simulations have expanded our understanding of these lipid–channel interactions, revealing lipids as active modulators rather than passive structural components. This review provides a comprehensive overview of the principles by which lipids regulate ion channel function and highlights the biological and potential clinical significance of this fundamental interplay.

Neurodegenerative conditions such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis (ALS) are devastating disorders with the gradual loss of neurons and cognitive or motor disability. This is a review article that develops the crucial functions of autophagy and proteostasis within the scope of the neurodegenerative disease. Autophagy is a very well-conserved cell process that poses a quality control checkpoint that allows for the degradation and recycling of damaged organelles and misfolded proteins. Chaperones, the ubiquitin–proteasome complexes, and endoplasmic reticulum-associated degradation (ERAD) are also referred to as proteostasis, which plays a key role in ensuring the correct protein folding properties and the prevention of toxic protein accumulation. This article offers a detailed discussion of the relationship between autophagy and proteostasis, illustrating the mechanisms of mutual cooperation of these processes, ensuring cellular homeostasis and inhibiting the formation of pathogenic protein aggregates. In addition, this review includes experimental data during preclinical studies and clinical trials and expounds on the therapeutic opportunities that show the potential of targeting autophagy and proteostasis to counter neurodegenerative disorders. Although research progress creates potential for new indicators, the issues and difficulties relating to the effects of regulating such complex cellular pathways are also discussed in the article. Finally, the review can add to the research of neurodegenerative disease mechanisms of autophagy and proteostasis as well as provide insights about the future of treatment and its implementation.

Peroxiredoxin 6 (Prdx6) is a bifunctional antioxidant enzyme with glutathione peroxidase and phospholipase A₂ activities that plays an essential role in cellular redox regulation. However, the modulation of Prdx6 activity by endogenous small metabolites remains poorly understood. In this study, we investigated the effect of β alanine on Prdx6 structure and function using biochemical, biophysical, computational, and cellular approaches. Enzymatic assays revealed that β alanine enhances the peroxidase activity of Prdx6 in a dose-dependent manner. Spectroscopic analyses demonstrated β alanine-induced conformational stabilization of Prdx6, which was further supported by increased thermal stability. Molecular docking and molecular dynamics simulations identified a stable interaction of β alanine at a distinct allosteric site on Prdx6, accompanied by reduced local flexibility. In a proof-of-concept cellular system, β alanine treatment resulted in a significant reduction in intracellular reactive oxygen species, consistent with enhanced Prdx6-associated antioxidant activity. Collectively, these findings identify β alanine as a biochemical modulator of Prdx6 activity. The study is limited to mechanistic and cellular redox regulation and does not address tissue- or disease-specific physiology.