Defects in sialic acid metabolism disrupt the sialylation of glycoproteins and glycolipids, contributing to a spectrum of diseases, including GNE myopathy (GNEM). This rare disorder is caused by mutations in the GNE gene that encodes for a bifunctional enzyme required for sialic acid biosynthesis, resulting in progressive muscle atrophy and weakness. There is no approved treatment for GNEM, and the number of affected individuals is underestimated. Although hyposialylation is considered the hallmark of GNEM, evidence showed lack of consistent correlation with GNEM severity and unveiled additional roles of GNE that contribute to the onset and/or progression of GNEM. Recent findings indicate that these mechanisms extend beyond glycosylation, encompassing cytoskeletal dynamics, oxidative stress, and muscle regeneration pathways. Understanding how GNE mutations result in a cascade of cellular and molecular dysregulations is crucial for developing targeted therapies aimed at improving the quality of life of patients. This review comprehensively examines GNEM's pathophysiology, clinical presentation, and therapeutic strategies, highlighting key findings on non-canonical GNE functions that account to GNEM clinical outcomes and emerging therapeutic targets. We propose future research directions to explore alternative target pathways that can ultimately support clinical development.

Background: The use of plants for therapeutic purposes has been supported by growing scientific evidence. Methods: This work consisted of (i) characterizing the phenolic compounds present in both aqueous and hydroethanol (1:1, v/v) extracts of camel grass, by hyphenated liquid chromatographic techniques, (ii) evaluating their anti-inflammatory, antioxidant, and neuromodulation potential, through in vitro cell and cell-free models, and (iii) establishing a relationship between the chemical profiles of the extracts and their biological activities. Results: Several caffeic acid and flavonoid derivatives were determined in both extracts. The extracts displayed scavenging capacity against the physiologically relevant nitric oxide (^•NO) and superoxide anion (O₂^•−) radicals, significantly reduced NO production in lipopolysaccharide (LPS)-stimulated macrophages (RAW 264.7), and inhibited the activity of hyaluronidase (HAase), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Some of these bioactivities were found to be related with the chemical profile of the extracts, namely with 3-caffeoylquinic, 4-caffeoylquinic, chlorogenic, and p-coumaric acids, as well as with luteolin and apigenin derivatives. Conclusions: This study reports, for the first time, the potential medicinal properties of aqueous and hydroethanol extracts of camel grass in the RAW 264.7 cell model of inflammation, and in neurologically related conditions.

The worldwide prevalence of obesity impacts more than 600 million adults. Successfully managing weight is effective in reducing the risk of chronic diseases, but sustaining long-term weight loss remains a challenge. Although there are supplements based on algae that claim to aid in weight loss, there is a notable scarcity of scientific evidence supporting their effectiveness, and their regular consumption safety remains inadequately addressed. In this work, commercially available Arthrospira (Spirulina) platensis Gomont and/or Fucus vesiculosus L. supplements showed moderate capacity to inhibit the activity of carbohydrate-metabolizing enzymes, and to scavenge biologically relevant reactive species. IC₂₅ values varying between 4.54 ± 0.81 and 66.73 ± 5.91 µg of dry extract/mL and between 53.74 ± 8.42 and 1737.96 ± 98.26 µg of dry extract/mL were obtained for α-glucosidase and aldose reductase, respectively. A weaker effect towards α-amylase activity was observed, with a maximum activity of the extracts not going beyond 33%, at the highest concentrations tested. Spirulina extracts showed generally better effects than those from F. vesiculosus. Similar results were observed concerning the antiradical capacity. In a general way, the extracts were able to intercept the in vitro-generated reactive species nitric oxide (^•NO) and superoxide anion (O₂^•−) radicals, with better results for O₂^•−scavenging with the spirulina samples (IC₂₅ values of 67.16 and 122.84 µg of dry extract/mL). Chemically, similar pigment profiles were observed between spirulina supplements and the authenticated counterpart. However, fucoxanthin, the chemotaxonomic marker of brown seaweeds, was not found in F. vesiculosus samples, pointing to the occurrence of a degradation phenomenon before, during, or after raw material processing. Our findings can contribute to providing data to allow regulatory entities (e.g., EFSA and FDA) to better rule these products in a way that can benefit society.

GNE myopathy (GNEM) is a rare disease clinically characterized by progressive muscle atrophy and weakness. Besides the rare incidence of the disease, the limited preclinical models are among the major bottlenecks for a better pathophysiological understanding of GNEM. This work aimed then at exploring the immunological context of GNEM in a recently established cell model. Our main findings suggest the involvement of an immune adaptive response, pointing to new alternative biological targets behind GNEM pathomechanisms.