1,721,078 research outputs found
Interactive role of Arf1 and Alpha tubulin-1 protein during the intracellular transportation of PrPc
No full textBehavioral abnormalities in prion protein knockout mice and the potential relevance of PrPC for the cytoskeleton
No full textThe cellular prion protein (PrPC) is a highly conserved protein, which is anchored to the outer surface of the plasma membrane. Even though its physiological function has already been investigated in different cell or mouse models where PrPC expression is either upregulated or depleted, its exact physiological role in a mammalian organism remains elusive. Recent studies indicate that PrPC has multiple functions and is involved in cognition, learning, anxiety, locomotion, depression, offensive aggression and nest building behavior. While young animals (3 months of age) show only marginal abnormalities, most of the deficits become apparent as the animals age, which might indicate its role in neurodegeneration or neuroprotection. However, the exact biochemical mechanism and signal transduction pathways involving PrPC are only gradually becoming clearer. We report the observations made in different studies using different Prnp0/0 mouse models and propose that PrPC plays an important role in the regulation of the cytoskeleton and associated proteins. In particular, we showed a nocodazole treatment influenced colocalization of PrPC and tubulin 1. In addition, we confirmed the observed deficits in nest building using a different backcrossed Prnp0/0 mouse line
Unveiling the Physical and Functional Niches of FAM26F by Analyzing Its Subcellular Localization and Novel Interacting Partners
No full textTherapeutic Potential of Amyloid‐β Interactors in Rapidly Progressive Alzheimer's Disease—An In Silico Study
No full textRapidly progressive Alzheimer's disease (rpAD) is a rare but severe form of Alzheimer's disease characterized by accelerated cognitive decline and limited therapeutic options. Conventional anti–amyloid‐β interventions have shown little success due to poor target specificity, neurotoxicity, and lack of efficacy, underscoring the need for novel therapeutic strategies. This study aimed to identify and prioritize molecular targets associated with rpAD by investigating the protein interactome of amyloid‐β (Aβ 42 ) using integrative computational approaches. Functional enrichment, protein–protein interaction network analysis, and community clustering revealed that rpAD‐specific Aβ 42 interactors were predominantly involved in mitochondrial bioenergetics, redox regulation, and cytoskeletal stability, pathways central to neuronal survival and synaptic function. Molecular docking identified fumarate hydratase, carbonyl reductase 1, and the F‐actin capping protein as high‐affinity interactors of Aβ 42 , linking these proteins to energy failure, oxidative stress, and synaptic dysfunction. Virtual screening of a therapeutic drug library against fumarate hydratase identified several compounds with strong binding affinities, among which quinestrol, estradiol benzoate, norethindrone, tamibarotene, drospirenone, and ketanserin emerged as lead candidates. Pharmacokinetic profiling, including ADMET modeling, confirmed their blood–brain barrier permeability and drug‐likeness, supporting their potential as central nervous system active agents. Together, this work highlights key molecular targets in rpAD and proposes repurposed, pharmacologically diverse compounds with multitarget neuroprotective potential. By utilizing in silico analysis, the study provides a rational framework for target discovery and drug prioritization in rpAD, offering a foundation for future experimental validation and the development of translational research
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