Types of memory, dementia, Alzheimer’s disease, and their various pathological cascades as targets for potential pharmacological drugs

Ageing Research Reviews, Год журнала: 2024, Номер 96, С. 102289 - 102289

Опубликована: Апрель 1, 2024

Язык: Английский

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CSF protein ratios with enhanced potential to reflect Alzheimer’s disease pathology and neurodegeneration

Molecular Neurodegeneration, Год журнала: 2024, Номер 19(1)

Опубликована: Фев. 13, 2024

Abstract Background Amyloid and tau aggregates are considered to cause neurodegeneration consequently cognitive decline in individuals with Alzheimer’s disease (AD). Here, we explore the potential of cerebrospinal fluid (CSF) proteins reflect AD pathology decline, aiming identify biomarkers for monitoring outcomes disease-modifying therapies targeting these aggregates. Method We used a multiplex antibody-based suspension bead array measure levels 49 CSF from Swedish GEDOC memory clinic cohort at Karolinska University Hospital. The comprised 148 amyloid- tau-negative (A-T-) 65 tau-positive (A+T+). An independent sample set 26 A-T- A+T+ Amsterdam Dementia Cohort was validation. measured were clustered based on their correlation amyloid beta peptides, NfL levels. Further, support vector machine modelling protein pairs, matched cluster origin, that improved performance compared single proteins. Results protein-clustering revealed 11 strongly correlated t-tau p-tau (tau-associated group), including mainly synaptic previously found elevated such as NRGN, GAP43 SNCB. Another 16 showed predominant Aβ42 (amyloid-associated PTPRN2, NCAN CHL1. Support two groups combined pairs discriminated higher accuracy proteins, well composed originating same group. Moreover, combining different ratios protein/amyloid-associated protein) significantly increased scores. results validated an cohort. Conclusions Combining brain-derived largely enhanced capacity discriminate between pathology-affected unaffected potentially due adjustment inter-individual variability. With results, highlight monitor thereby possibly efficacy therapies.

Язык: Английский

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Brain-specific targeted delivery of therapeutic agents using metal–organic framework-based nanomedicine

Coordination Chemistry Reviews, Год журнала: 2024, Номер 514, С. 215926 - 215926

Опубликована: Май 9, 2024

Язык: Английский

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Aβ42 and ROS dual-targeted multifunctional nanocomposite for combination therapy of Alzheimer’s disease

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Май 23, 2024

Abstract Amyloid-β (Aβ) readily misfolds into neurotoxic aggregates, generating high levels of reactive oxygen species (ROS), leading to progressive oxidative damage and ultimately cell death. Therefore, simultaneous inhibition Aβ aggregation scavenging ROS may be a promising therapeutic strategy alleviate Alzheimer’s disease pathology. Based on the previously developed antibody 1F12 that targets all forms 42 , we an dual-targeting nanocomposite using biodegradable mesoporous silica nanoparticles as carriers load ultra-small cerium oxide nanocrystals (bMSNs@Ce-1F12). By modifying brain-targeted rabies virus glycoprotein 29 (RVG29-bMSNs@Ce-1F12), this intelligent can efficiently target brain Aβ-rich regions. Combined with peripheral central nervous system treatments, RVG29-bMSNs@Ce-1F12 significantly AD symptoms by inhibiting misfolding, accelerating clearance, ROS. Furthermore, synergistic effect clearance exhibited dual-targeted also reduced burden hyperphosphorylated tau, alleviated glial activation, improved cognitive function in APP/PS1 mice. Our findings indicate is nanodrug facilitate multi-target treatment AD.

Язык: Английский

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Effect of the ROCK inhibitor fasudil on the brain proteomic profile in the tau transgenic mouse model of Alzheimer's disease

Frontiers in Aging Neuroscience, Год журнала: 2024, Номер 16

Опубликована: Фев. 19, 2024

Introduction The goal of this study is to explore the pharmacological potential amyloid-reducing vasodilator fasudil, a selective Ras homolog (Rho)-associated kinases (ROCK) inhibitor, in P301S tau transgenic mouse model (Line PS19) neurodegenerative tauopathy and Alzheimer's disease (AD). Methods We used LC-MS/MS, ELISA bioinformatic approaches investigate effect treatment with fasudil on brain proteomic profile PS19 mice. also explored efficacy reducing phosphorylation, beneficial and/or toxic effects its administration Results Proteomic profiling mice brains exposed revealed activation mitochondrial tricarboxylic acid (TCA) cycle blood-brain barrier (BBB) gap junction metabolic pathways. observed significant negative correlation between levels phosphorylated (pTau) at residue 396 both metabolite hydroxyfasudil. Conclusions Our results provide evidence proteins pathways related mitochondria BBB functions by support further development therapeutic for AD.

Язык: Английский

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