Institute for Advanced Studies in Basic Sciences

Alpha-synuclein (α-Syn) is a neuronal protein implicated in the pathogenesis of several neurodegenerative disorders collectively known as synucleinopathies, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. This article provides a comprehensive overview of the structural characteristics of α-Syn, emphasizing its fibrillar aggregation and the resulting polymorphic fibril forms. Using advances in cryo-electron microscopy, a diverse range of α-Syn fibril polymorphs has been elucidated, both from in vitro preparations and patient-derived brain samples. We further explore the impact of mutation and post-translational modifications-such as truncation and phosphorylation -on α-Syn structure and the unique polymorphs they induce. The article underscores the biological and pathological relevance of α-Syn polymorphism, highlighting how different structural strains may underlie the structural and pathological heterogeneity observed in synucleinopathies. Understanding the mechanisms driving polymorph formation is critical for deciphering disease progression and developing targeted therapeutic strategies.

An increasing body of evidence suggests that mitochondrial dysfunction mediated by α-synuclein (α-syn) aggregates plays a key role in the pathogenesis of Parkinson's disease (PD), leading to intensive research for the discovery and development of compounds with mitoprotective effects. Silymarin (SIL) is a complex mixture of flavonolignans with a wide range of protective effects on mitochondria under stress conditions. Herein, the potency of SIL, in bulk and nano forms, in protecting mitochondria against oxidative damage induced by α-syn aggregates has been investigated. Mitochondria were isolated from rat brain and liver tissues as well as human neuroblastoma SH-SY5Y cells, and damage was evaluated by using a range of biochemical assays. The obtained results show a substantial difference in the response of various mitochondria to oxidative damage induced by α-syn aggregates, with brain mitochondria exhibiting the highest vulnerability. We found that incubation of mitochondria with either bulk or nano forms of SIL before exposure to α-syn aggregates significantly attenuated oxidative damage in a dose-dependent manner. In parallel, α-syn aggregates aged in the presence of bulk or nano forms of SIL considerably lost their capacity to cause mitochondrial damage. While both bulk and nano forms of SIL showed significant mitoprotective effects, SIL nanosheets were much more effective. Possible mechanisms relating to the mitoprotective effects of SIL and the higher efficacy of SIL nanosheets are discussed. The obtained results suggest natural polyphenol-based nanoparticles as an efficient therapeutic approach in relation to amyloid-related diseases, such as PD.

ABSTRACT Canola ( Brassica napus L.) seeds are small and exhibit significant variability in size, resulting in a decreased emergence percentage (EP) and reduced uniformity in the field. Additionally, canola seedlings are susceptible to Rhizoctonia solani in the early growth stages. This research aimed to investigate the effects of seed pelleting with different fillers, binders and biomaterials on canola's emergence quality, early growth and seedling health. The first experiment was conducted in the seed laboratory and greenhouses. The treatments included four types of fillers: calcium sulphate + zeolite (CS + Z), calcium sulphate + talc (CS + T), calcium sulphate + calcium carbonate (CS + CC) and calcium carbonate + bentonite (CC + B). Additionally, three types of binder materials were evaluated: gum arabic, selenium dioxide and carboxymethylcellulose. The results showed that the composition of carboxymethylcellulose as a binder, combined with a filler mixture of calcium sulphate and calcium carbonate, significantly increased the emergence rate and early growth compared to non‐pelleted seeds. Furthermore, this seed pelleting treatment did not adversely affect seed emergence. The highest emergence rate (0.185), leaf area (3.94 cm 2 ), shoot growth rate (0.019 cm day −1 ), leaf chlorophyll content (41.03), plant length vigour index (3543), root value (1.35) and plant weight vigour index (26.66) were observed in seeds pelleted with a composition of CS + CC (200 g calcium sulphate + 50 g calcium carbonate per 10 g seed −1 ), and carboxymethylcellulose (30 g carboxymethylcellulose per 10 g seed −1 ). Because the seeds pelleted with this combination had the highest sphericity, pelleting efficiency and the lowest fragmentation number and dissolution time. The second experiment evaluated the effects of four levels (0, 500, 1000, 1500 and 2000 mg g −1 ) of extracts from Thymus vulgaris , Lavandula officinalis , Cinnamomum verum and Salvia rosmarinus . The results showed that T. vulgaris extract at a concentration of 2000 ppm significantly controlled the growth of R. solani . The third experiment was conducted in the seed laboratory and greenhouses. The treatments included pelleted seeds with the same superior treatment as in the first experiment (CS + CC (200 g/10 g −1 + 50 g/10 g −1 ) + CMC 2 (30 g/10 g −1 )), to which four medicinal plant extracts ( T. vulgaris , L. officinalis , C. verum and S. rosmarinus ) and five concentrations (0, 500, 1000, 1500 and 2000 ppm) were added. The results showed that the highest percentages of emergence (67%), emergence rate (0.085 seeds per day), leaf number (9.6), shoot dry weight (0.42 g), root dry weight (0.35 g) and seedling vigour index (57.49) were observed in seeds pelleted with 2000 ppm T. vulgaris extract. In conclusion, the use of a combination of calcium sulphate, calcium carbonate and carboxymethylcellulose for seed pelleting, alongside T. vulgaris extract as an environmentally friendly antifungal agent, has been shown to enhance the quality of canola seeds and improve the disease resistance of canola seedlings in soils infested with R. solani .

Allergic diseases affect over one billion people worldwide as a common chronic condition. Conventional treatments often relieve symptoms but lack long-term efficacy or safety. Over the past decade, nanomedicine, i.e., nanoscale drugs and delivery systems, has emerged as a promising alternative that leverages the tunable physicochemical properties of nanoparticles (NPs) and enhances both diagnosis and treatment of hypersensitivity disorders. In diagnostics, nanoparticle-based biosensors have achieved detection limits as low as 42 fg/mL with specificity exceeding 90% for food and aeroallergen proteins. Therapeutic applications comprise various NPs, including gold, silver, iron oxide, carbon-based, lipid-mediated, polymeric, dendrimeric, and virus-like, as delivery vehicles and as immunomodulators. Preclinical models detect >50% reductions in pro-inflammatory cytokines (IL-4, IL-5) and two- to 3-fold reductions in eosinophil infiltration following NP-augmented allergen immunotherapy, with antigen-specific IgE titers reduced by up to 70%. Although such advancement has occurred, nanotoxicology studies highlight dose-dependent organ concentration and prolonged pulmonary half-lives that necessitate rigorous biosafety evaluation. Regulatory and manufacturability concerns remain significant hurdles for clinical translation. This article reviews up-to-date quantitative performance metrics for nanoparticle therapeutics and diagnostics in allergy control, critically examines the toxicity profiles and translational issues, and brings out directions toward individualized, safe nanotheranostic platforms.