Precision drug delivery to the central nervous system using engineered nanoparticles

Nature Reviews Materials, Год журнала: 2024, Номер 9(8), С. 567 - 588

Опубликована: Июнь 25, 2024

Язык: Английский

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Polycatechols inhibit ferroptosis and modulate tau liquid–liquid phase separation to mitigate Alzheimer's disease

Materials Horizons, Год журнала: 2024, Номер 11(13), С. 3082 - 3089

Опубликована: Янв. 1, 2024

Polycatechols modulate amyloid-associated toxicities, arrest labile iron, inhibit lipid peroxidation, and regulate tau liquid–liquid phase separation (LLPS) to mitigate the pathological nexus between ferroptosis AD.

Язык: Английский

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Transcranial alternating current stimulation (tACS) at gamma frequency: an up-and-coming tool to modify the progression of Alzheimer’s Disease

Translational Neurodegeneration, Год журнала: 2024, Номер 13(1)

Опубликована: Июнь 27, 2024

Abstract The last decades have witnessed huge efforts devoted to deciphering the pathological mechanisms underlying Alzheimer’s Disease (AD) and testing new drugs, with recent FDA approval of two anti-amyloid monoclonal antibodies for AD treatment. Beyond these drug-based experimentations, a number pre-clinical clinical trials are exploring benefits alternative treatments, such as non-invasive stimulation techniques on neuropathology symptoms. Among different brain approaches, transcranial alternating current (tACS) is gaining particular attention due its ability externally control gamma oscillations. Here, we outline knowledge concerning efficacy, safety, ease-of-use cost-effectiveness tACS early advanced AD, applied specifically at 40 Hz frequency, also summarise results validated models ongoing patient-centred trials.

Язык: Английский

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Cognitive performance in aged rats is associated with differences in distinctive neuronal populations in the ventral tegmental area and altered synaptic plasticity in the hippocampus

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

Опубликована: Фев. 26, 2024

Introduction Deterioration of cognitive functions is commonly associated with aging, although there wide variation in the onset and manifestation. Albeit heterogeneity age-related decline has been studied at cellular molecular level, poor evidence for electrophysiological correlates. The aim current study was to address basis cognitively Inferior Superior old (19-20 months) rats ventral tegmental area (VTA) hippocampus, having Young (12 weeks) as a control. midbrain VTA operates hub amidst affective facets, processing sensory inputs related motivated behaviours hippocampal memory. Increasing shows direct dopaminergic non-dopaminergic input from hippocampus. Methods Aged male were selected cohort 88 animals based on their performance spatial learning memory task. Using vivo single-cell recording VTA, we examined electrical activity different neuronal populations (putative dopaminergic, glutamatergic GABAergic neurons). In same animals, basal synaptic transmission plasticity slices. Results Electrophysiological recordings hippocampus showed alterations aging per se , together differences specifically linked status aged animals. particular, bursting dopamine neurons lower, while firing frequency higher rats. response high-frequency stimulation slices also discriminated between Discussion This provides new insight into information underlying compromised cerebral ageing. Further understanding brain senescence, possibly neurocognitive decline, will help develop strategies towards preservation high quality life.

Язык: Английский

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Photostimulation of Locus Coeruleus CA1 catecholaminergic terminals reversed spatial memory impairment in an Alzheimer's disease mouse model.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

Rationale One of the earliest changes associated with Alzheimer's disease (AD) is loss catecholaminergic terminals in cortex and hippocampus originating from Locus Coeruleus (LC). This decline leads to reduced neurotransmitters hippocampus, affecting synaptic plasticity spatial memory. However, it unclear whether restoring transmission LC may alleviate memory deficits AD. Objectives study investigates how optogenetic stimulation projections locus coeruleus hippocampal CA1 region enhance disease. Methods We conducted experiments using a 12-month-old 3xTg-AD mouse model (AD-TH), which expresses Cre recombinase under control tyrosine hydroxylase (TH) gene. allowed us photostimulate before performing two different tasks inducing long-term potentiation (LTP). Results Optogenetic successfully reversed impairment retrieval aging AD-TH mice. Furthermore, this restored neurotransmitter levels enhanced plasticity, as demonstrated by an LTP protocol. Conclusions These findings indicate that circuitry (LC) plays crucial role disrupting contributing seen early stages highlights potential therapeutic benefits targeting neurons improve cognitive function patients

Язык: Английский

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Pharmacological reduction of reverse-translated hippocampal hyperactivity in mouse: relevance for psychosis

Neuropsychopharmacology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

Язык: Английский

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Repetitive prefrontal tDCS activates VTA dopaminergic neurons, resulting in attenuation of Alzheimer’s Disease-like deficits in Tg2576 mice

Alzheimer s Research & Therapy, Год журнала: 2025, Номер 17(1)

Опубликована: Апрель 29, 2025

Язык: Английский

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Association between the use of levodopa/carbidopa, Alzheimer's disease biomarkers, and cognitive decline among participants in the National Alzheimer's Coordinating Center Uniform Data Set

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(5)

Опубликована: Май 1, 2025

Abstract INTRODUCTION This retrospective study investigates whether exposure to levodopa/carbidopa (LA/CA) medication is associated with modified Alzheimer's disease (AD) trajectories. METHODS Multivariate analysis used cerebrospinal fluid (CSF) biomarker information included in the National Coordinating Center Uniform Data Set for subjects normal cognition (NC), mild cognitive impairment (MCI), and dementia (DE). Survival analyses examined progression MCI/DE death events. RESULTS LA/CA use lower levels of CSF amyloid beta, phosphorylated‐tau (p‐tau) total‐tau. After adjusting age, sex, apolipoprotein E (APOE) ε4 allele presence, that effect was quantified by negative coefficients fitted linear mixed models: p ‐values < 0.01 all cases except p‐tau MCI subgroup ( = 0.02). No similar effects were identified other antiparkinsonians. Exposure decreased from DE 0.03). DISCUSSION The association between exposure, AD biomarkers, deserves further investigation controlled clinical trials. Highlights biomarkers AD. not observed when antiparkinsonian drugs are used. also delayed patients MCI.

Язык: Английский

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Activation of AMPK by GLP-1R agonists mitigates Alzheimer-related phenotypes in transgenic mice

Nature Aging, Год журнала: 2025, Номер unknown

Опубликована: Май 20, 2025

Язык: Английский

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Prophylactic treatment with the c-Abl inhibitor, neurotinib, diminishes neuronal damage and the convulsive state in pilocarpine-induced mice

Cell Reports, Год журнала: 2024, Номер 43(5), С. 114144 - 114144

Опубликована: Апрель 23, 2024

The molecular mechanisms underlying seizure generation remain elusive, yet they are crucial for developing effective treatments epilepsy. current study shows that inhibiting c-Abl tyrosine kinase prevents apoptosis, reduces dendritic spine loss, and maintains N-methyl-d-aspartate (NMDA) receptor subunit 2B (NR2B) phosphorylated in vitro models of excitotoxicity. Pilocarpine-induced status epilepticus (SE) mice promotes phosphorylation, disrupting activity leads to fewer seizures, increases latency toward SE, improved animal survival. Currently, clinically used inhibitors non-selective have poor brain penetration. allosteric inhibitor, neurotinib, here has favorable potency, selectivity, pharmacokinetics, vastly Neurotinib-administered seizures survival following pilocarpine-SE induction. Our findings reveal activation as a key factor ictogenesis highlight the impact its inhibition preventing insurgence epileptic-like rodents humans.

Язык: Английский

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