Modern light microscopy, including super-resolution techniques, has brought about a demand for small labeling tags that bring the fluorophore closer to the target. This challenge can be addressed by labeling unnatural amino acids (UAAs) with bioorthogonal click chemistry. The minimal size of the UAA and the possibility to couple the fluorophores directly to the protein of interest with single-residue precision in living cells make click labeling unique. Here, we establish click labeling in living primary neurons and use it for fixed-cell, live-cell, dual-color pulse–chase, and super-resolution microscopy of neurofilament light chain (NFL). We also show that click labeling can be combined with CRISPR/Cas9 genome engineering for tagging endogenous NFL. Due to its versatile nature and compatibility with advanced multicolor microscopy techniques, we anticipate that click labeling will contribute to novel discoveries in the neurobiology field.

Parkinson’s disease-associated kinase LRRK2 has been linked to IFN type II (IFN-γ) response in infections and to dopaminergic neuronal loss. However, whether and how LRRK2 synergizes with IFN-γ remains unclear. In this study, we employed dopaminergic neurons and microglia differentiated from patient-derived induced pluripotent stem cells carrying LRRK2 G2019S, the most common Parkinson’s disease-associated mutation. We show that IFN-γ enhances the LRRK2 G2019S-dependent negative regulation of AKT phosphorylation and NFAT activation, thereby increasing neuronal vulnerability to immune challenge. Mechanistically, LRRK2 G2019S suppresses NFAT translocation via calcium signaling and possibly through microtubule reorganization. In microglia, LRRK2 modulates cytokine production and the glycolytic switch in response to IFN-γ in an NFAT-independent manner. Activated LRRK2 G2019S microglia cause neurite shortening, indicating that LRRK2-driven immunological changes can be neurotoxic. We propose that synergistic LRRK2/IFN-γ activation serves as a potential link between inflammation and neurodegeneration in Parkinson’s disease.

Background:: Pomegranate (Punica granatum L.) fruits are widely consumed and used as preventive and therapeutic agents since ancient times. Pomegranate is a rich source of a variety of phytochemicals, which are responsible for its strong antioxidative and anti-inflammatory potential. Objective:: The aim of this review is to provide an up-to-date overview of the current knowledge of chemical structure and potential health benefits of pomegranate. Method: : A comprehensive search of available literature. Results:: The review of the literature confirms that juice and extracts obtained from different parts of this plant, including fruit peel, seeds, and leaves exert health benefits in both in vitro and in vivo studies. The antidiabetic, antihypertensive, antimicrobial and anti-tumour effects of pomegranate fruit are of particular scientific and clinical interest. Conclusion:: Further investigations are required to clarify the mechanism of action of the bioactive ingredients and to reveal full potential of pomegranate as both preventive and therapeutic agent.

Being characterized by progressive and severe damage in neuronal cells, neurodegenerative diseases (NDDs) are the major cause of disability and morbidity in the elderly, imposing a significant economic and social burden. As major components of the central nervous system, lipids play important roles in neural health and pathology. Disturbed lipid metabolism, particularly lipid peroxidation (LPO), is associated with the development of many NDDs, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), all of which show elevated levels of LPO products and LPO-modified proteins. Thus, the inhibition of neuronal oxidation might slow the progression and reduce the severity of NDD; natural antioxidants, such as polyphenols and antioxidant vitamins, seem to be the most promising agents. Here, we summarize current literature data that were derived from human studies on the effect of natural polyphenols and vitamins A, C, and E supplementation in patients with AD, PD, and ALS. Although these compounds may reduce the severity and slow the progression of NDD, research gaps remain in antioxidants supplementation in AD, PD, and ALS patients, which indicates that further human studies applying antioxidant supplementation in different forms of NDDs are urgently needed.