Biology subjects

Alim, A.

Publications and source records attributed to Alim, A..

4 recordsLinked to original sources

bioRxiv2026

Aβ42-Driven α-synuclein Fibril Polymorphism and Distinct Intracellular Aggregation

The frequent coexistence of -synuclein (-syn) and amyloid-{beta} (A{beta}) aggregates in neurodegenerative diseases suggests that heterotypic interactions between these amyloidogenic proteins may influence disease progression, yet their molecular consequences remain poorly understood. Here, we investigated how distinct aggregation states of A{beta}42, monomers and preformed fibrils (PFFs), modulate -syn fibril formation, structure, and downstream neuronal pathology. Thioflavin T kinetics showed that A{beta}42 monomers delayed -syn fibril formation, whereas A{beta}42 PFFs exhibited a trend toward accelerated aggregation, indicating aggregation state-dependent effects on -syn aggregation. Negative-stain TEM, proteinase K digestion, and solid-state NMR spectroscopy further demonstrated that both A{beta}42 monomers and PFFs altered -syn fibril structure, generating distinct fibril conformations depending on the A{beta}42 concentration and aggregation state. To determine whether these conformational differences influence pathological activity, -syn PFF variants generated in the presence of different concentrations of A{beta}42 monomers or PFFs were applied to dopaminergic neuronal cells. -Syn fibrils formed in the presence of A{beta}42 PFFs showed greater capacity to induce intraneuronal -syn aggregation than -syn PFFs, whereas fibrils formed in the presence of A{beta}42 monomers exhibited similar or reduced seeding capacity relative to -syn PFFs. Together, our findings demonstrate that heterotypic interactions with A{beta}42 reshape -syn aggregation pathways and fibril conformations, generating structurally distinct -syn fibril populations with different neuronal seeding activities. These results provide a molecular framework for understanding how cross-talk between amyloidogenic proteins may contribute to structural and pathological heterogeneity in mixed neurodegenerative diseases.

molecular biology↗

bioRxiv2025

Impact of Membrane Fluidity on α-syn Fibril Structures and Neuronal Pathology

Conformational variations in -syn fibrils are thought to underlie the distinct clinical features of synucleinopathies, including Lewy body dementia (LBD), Parkinsonss disease (PD), and multiple system atrophy (MSA), suggesting that distinct fibril structures act as molecular fingerprints linked to disease phenotype. While the origins of these conformational variations remain unclear, increasing evidence points to membranes as key modulators of fibrils conformations. In this study, we investigated how age-related alterations in membrane composition and fluidity influence -syn fibril formation and cellular outcomes. Using complex mixture membranes that mimic normal neuronal membranes and their age-related modifications in fatty acid chains, we found that -syn fibrils grown with these membranes displayed distinct 2D ssNMR spectral patterns compared to lipid-free -syn fibrils, reflecting differences in rigid fibril cores. Moreover, fibrils grown with age-related membranes exhibited weaker membrane association than those grown with normal neuronal membranes. These membrane-associated fibrils induce stronger neuronal pathologies than lipid-free fibrils, though the severity differed in intraneuronal aggregation and inflammation responses. Overall, our findings provide new insights into how age-related changes in membrane composition shape -syn fibril structure and pathogenicity, strengthening the link between membrane dynamics and amyloid-driven neurodegeneration.

molecular biology↗

bioRxiv2025

Microphysiological engineering of the capillary interface of substantia nigra dopaminergic neurons to study vascular alterations in Parkinson's Disease

Parkinsons Disease (PD) is primarily characterized by -synuclein pathology, which manifests as intraneuronal inclusions, neuroinflammation, and neurodegeneration. However, emerging evidence also points to significant vascular impairments as a critical aspect of PD pathology, which remains largely underexplored due to the inability of traditional in vitro models to recapitulate such vascular changes. To address this unmet need, here we combine the human organ-on-a-chip technology with the principle of vasculogenic self-assembly to engineer the capillary interface of dopaminergic neurons in the substantia nigra pars compacta of the midbrain. In our proof-of-concept demonstration, we successfully recreated critical neuronal pathology in PD, including -synuclein aggregation, inflammatory responses, and progressive neuronal degeneration, by exposing our model to specially generated PD-associated -synuclein preformed fibrils. Importantly, this engineering approach also enables the investigation of progressive vascular changes characteristic of PD, such as endothelial dysfunction, barrier disruption, and vascular regression. Our sophisticated PD model establishes a novel platform for exploring the multifaceted nature of the disease and understanding the complex interplay between neurodegeneration and vascular pathology, offering a unique tool for developing innovative therapeutic strategies that address both the neuronal and vascular components of PD pathology.

bioengineering↗

bioRxiv2025

Analysis of aroma compounds in Barbecued Mutton (Kebab) during different storage periods and exploration of customer preferences

Kebab (barbecued mutton) is a traditional meat product with a rich roasted meaty aroma and is highly favored by consumers. However, there are no reports on the flavor changes of different roasted meat tissues during storage, and there are no studies on why consumers prefer to eat Kebab. This study employed GC-IMS to explore the changes in aroma compounds in Kebab. Simultaneously, molecular docking was used to explore the mechanism of aroma compounds that trigger pleasure and to infer the optimal storage methods. A total of 61 volatile compounds, including aldehydes, alcohols, esters, ketones, acids, furans, ethers, and terpenes, were identified. Sensory evaluation revealed that when the storage time increased, the sour and sulfur aromas of mutton were strong, whereas the fatty aroma significantly increased and decreased in fat and lean meat. Additionally, a sense of pleasure was speculated by exemplifying six key aroma compounds. The differences in aroma compounds in the Kebab samples were clearly observed and indicated that the lean meat kebab maintained numerous meaty aroma compounds during storage until the 28th day. This is the first study to reveal the potential mechanism of the pleasure generated by eating Kebab, which will provide practical application value for evaluating the flavor of Kebab.

biochemistry↗