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Non-covalent van der Waals interactions play a major role at the nanoscale, and even a slight change in their asymptotic decay could produce a major impact on surface phenomena, self-assembly of nanomaterials, and biological systems. By a full many-body description of vdW interactions in coupled carbyne-like chains and graphenic structures, here, we demonstrate that both modulus and a range of interfragment forces can be effectively tuned, introducing mechanical strain and doping (or polarizability change). This result contrasts with conventional pairwise vdW predictions, where the two-body approximation essentially fixes the asymptotic decay of interfragment forces. The present results provide viable pathways for detailed experimental control of nanoscale systems that could be exploited both in static geometrical configurations and in dynamical processes. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a prevalent neurodegenerative disease associated with dementia and neuronal impairments in brain. AD is characterized histopathologically by two hallmark lesions: abnormally phosphorylated Tau inside neurons as intracellular NFTs and extracellular accumulation of amyloid β peptide (Aβ). Furthermore, it is unable to clarify the distinction between the brief association between the development and build-up of Aβ and the commencement of illness. Additionally, a number of experimental findings suggest that symptoms related to Aβ may only manifest within the framework of anabatic Tauopathies. Tau, a natively unfolded protein, essentially involved in microtubule binding and assembly. Tau protein consists of truncated segment and the purpose of this truncated fragment is to initiate and promote the conversion of soluble Tau into aggregates. The most common aberrant posttranslational change found in Neuro Fibrillary Tangles is hyperphosphorylation, which is essentially composed of aggregated Tau. Tau phosphorylation and acetylation of Tau protein at the locations controlled by histone deacetylase 6 compete, which modulates Tau function. Considering the potential benefits of targeting HDAC6 in AD, we propose focusing on the role of HDAC6 in regulating Tau functions and the other targets are the therapeutic understanding of AD., (Copyright © 2025. Published by Elsevier Inc.)

Lipids play an essential role in synaptic function, significantly impacting synaptic physiology through their dynamic nature and signaling capabilities. Membrane lipids, including cholesterol, phospholipids, and gangliosides, are crucial for synaptic organization and function. They act as structural integrators and signaling molecules, guiding vesicle intracellular movement and regulating enzyme activity to support neuronal activity. The lipid compositions of pre-synaptic and post-synaptic membranes influence vesicle generation and receptor mobility, highlighting their active involvement in synaptic processes. Astrocytes also contribute to synaptic health by upholding the blood-brain barrier, regulating ion levels, and providing metabolic support. Lipid-mediated processes control synaptic plasticity and development, with astrocytes playing a crucial role in glutamate homeostasis. Amyloid-beta and Tau proteins are key in Alzheimer's disease (AD), where synaptic disruption leads to cognitive deficits. Clathrin-mediated endocytosis (CME) and caveolin-mediated endocytosis are critical pathways for lipid-mediated synaptic function, with disruptions in these pathways contributing to AD pathogenesis., (Copyright © 2025. Published by Elsevier Inc.)

The nuclear pore complex, a large multimeric structure consists of numerous protein components, serves as a crucial gatekeeper for the transport of macromolecules across the nuclear envelope in eukaryotic cells. Dysfunction of the NPC has been implicated in various neurodegenerative diseases, including Alzheimer's disease. In AD, Tau aggregates interact with NPC proteins, known as nucleoporins, leading to disruptions in nuclear transport. Hyperphosphorylated Tau, a hallmark of AD pathology, interacts with central channel NUPs such as Nup62 and Nup98, causing cytoplasmic mis-localization of these proteins and impairing nuclear transport. Furthermore, Tau-NUP interactions promote Tau aggregation and the formation of neurofibrillary tangles, exacerbating neurodegeneration. Oligomeric Tau adheres to the lamin B receptor as well as nuclear lamin, preventing nucleocytoplasmic transport and resulting in heterochromatin unwinding, DNA damage, and neuronal death. The decrease in lamin B and increasing levels of lamin A along with C in AD-affected brain areas highlight the disease's intricacy. Furthermore, Tau internalization in the nucleus and interaction with nuclear pore complexes worsen NPC dysfunction, which contributes to neurotoxicity. Tau-DNA interactions suggest a chaperone-like role for Tau in DNA organization and repair, highlighting its involvement in maintaining genomic integrity. This review explores the intricate relationships between Tau, NPC components, and nuclear lamin in the context of AD, providing insights into the mechanisms underlying Tau-induced neurodegeneration and potential therapeutic targets., (Copyright © 2025. Published by Elsevier Inc.)

The neuronal cytoskeleton has remained a less explored area of research in establishing neuroprotection. HDAC6 has been studied with respect to many neurodegenerative diseases, especially AD. It exhibits the ability to interact with various cytoskeletal proteins and to promote migration in cells. Podosomes are actin microstructures that help cells to migrate in the extracellular environment. The aim of this review is to bring into focus the significance of studies on the involvement of podosomes in Alzheimer's disease. We have suggested that Histone Deacetylase 6 plays a vital role in AD, through its interactions with the various signalling processes in the cell, most importantly the cytoskeletal remodelling machinery within the podosomes., (Copyright © 2025. Published by Elsevier Inc.)

Tau is a well-known microtubule-associated protein and is located in the cytoplasm of neurons, which play a crucial role in Alzheimer's diseases. Due to its preferred binding to DNA sequences found in the nucleolus and pericentromeric heterochromatin, Tau has been found within the cell nucleus, where it may be a nucleic acid-associated protein. Tau has the ability to directly interact with nuclear pore complex nucleoporins, influencing both their structural and functional integrity. The interaction between Tau and NUPs highlights a potential mechanism underlying NPC dysfunction in AD pathogenesis. Pathological Tau hinders the import and export of nucleus through RAN mediated cascades. Nuclear Tau aggregates colocalize with membrane less organelles called nuclear speckles, which are involved in pre-mRNA splicing, and modify their dynamics, composition, and structure. Additionally, SRRM2 and other nuclear speckle proteins including MSUT2 and PABPN1 mislocalize to cytosolic Tau aggregates, and causes propagation of Tau aggregates. Research highlights, Extracellular Tau Oligomers induce significant nuclear invagination. They act as a key player in the transformation of healthy neurons into sick neurons in AD. The mechanism behind this phenomenon depends on intracellular Tau and is linked to changes in chromatin structure, nucleocytoplasmic transport, and gene transcription. This review highlights the vital roles of nuclear Tau protein in the context of nuclear pore complex functioning and, modulation of nuclear speckles in Alzheimer's diseases. Addressing these pathways is essential for formulating focused therapeutics intended to alleviate Tau-induced neurodegeneration., (Copyright © 2025. Published by Elsevier Inc.)