Colistin treatment causes neuronal loss and cognitive impairment via ros accumulation and neuronal plasticity alterations.

The rise of antimicrobial resistance has made necessary the increase of the antibacterial arsenal against multidrug-resistant bacteria. In this context, colistin has re-emerged as a first-line antibiotic in critical situations despite its nephro- and neuro- toxicity at peripheral level. However, the mechanism underlying its toxicity remains unknown, particularly in relation to the central nervous system (CNS).

Unveiling the potential of intranasal delivery of renin-angiotensin system drugs: Insights on the pharmacokinetics of irbesartan.

The therapeutic interest of renin-angiotensin system (RAS) drugs for the treatment of neuroinflammation has been recently acknowledged. Nevertheless, most of them display limited passage across the blood-brain barrier (BBB). Therefore, this study investigated the potential of intranasal (IN) delivery of six RAS drugs to circumvent the BBB and attain the brain, envisioning its future use in central nervous system (CNS) neuroinflammatory diseases, such as Alzheimer's disease (AD).

From Inhalation to Neurodegeneration: Air Pollution as a Modifiable Risk Factor for Alzheimer's Disease.

Air pollution, a growing concern for public health, has been linked to various respiratory and cardiovascular diseases. Emerging evidence also suggests a link between exposure to air pollutants and neurodegenerative diseases, particularly Alzheimer's disease (AD). This review explores the composition and sources of air pollutants, including particulate matter, gases, persistent organic pollutants, and heavy metals.

JNK signaling and its impact on neural cell maturation and differentiation.

C-Jun-N-terminal-kinases (JNKs), members of the mitogen-activated-protein-kinase family, are significantly linked with neurological and neurodegenerative pathologies and cancer progression. However, JNKs serve key roles under physiological conditions, particularly within the central-nervous-system (CNS), where they are critical in governing neural proliferation and differentiation during both embryogenesis and adult stages. These processes control the development of CNS, avoiding neurodevelopment disorders.

Krüppel-like factors: potential roles in blood-brain barrier dysfunction and epileptogenesis.

Epilepsy is a chronic and debilitating neurological disorder, known for the occurrence of spontaneous and recurrent seizures. Despite the availability of antiseizure drugs, 30% of people with epilepsy experience uncontrolled seizures and drug resistance, evidencing that new therapeutic options are required. The process of epileptogenesis involves the development and expansion of tissue capable of generating spontaneous recurrent seizures, during which numerous events take place, namely blood-brain barrier (BBB) dysfunction, and neuroinflammation.

Effects of a High-Fat Diet on Insulin-Related miRNAs in Plasma and Brain Tissue in APP/PS1dE9 and Wild-Type C57BL/6J Mice.

Insulin resistance (IR)-related miRNAs have been associated with the development and progression of Alzheimer's disease (AD). The dietary modulation of these miRNAs could become a potential strategy to manage AD. The aim of this study was to evaluate the effect of a high-fat diet (HFD), which aggravates AD-related pathogenic processes, on serum, cortex and hippocampus IR-related miRNA expression.

Exploring small non-coding RNAs as blood-based biomarkers to predict Alzheimer's disease.

Background: Alzheimer's disease (AD) diagnosis relies on clinical symptoms complemented with biological biomarkers, the Amyloid Tau Neurodegeneration (ATN) framework. Small non-coding RNA (sncRNA) in the blood have emerged as potential predictors of AD. We identified sncRNA signatures specific to ATN and AD, and evaluated both their contribution to improving AD conversion prediction beyond ATN alone.

Intranasal irbesartan reverts cognitive decline and activates the PI3K/AKT pathway in an LPS-induced neuroinflammation mice model.

Background: New strategies are urgently needed to manage and delay the development of Alzheimer's disease (AD). Neuroinflammation is a significant contributor to cognitive decline in neurodegenerative diseases, including AD. Angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) protect hypertensive patients against AD, but the cellular and molecular mechanisms underlying these effects remain unknown.

Licochalcone A: A Potential Multitarget Drug for Alzheimer's Disease Treatment.

Licochalcone A (Lico-A) is a flavonoid compound derived from the root of the Glycyrrhiza species, a plant commonly used in traditional Chinese medicine. While the Glycyrrhiza species has shown promise in treating various diseases such as cancer, obesity, and skin diseases due to its active compounds, the investigation of Licochalcone A's effects on the central nervous system and its potential application in Alzheimer's disease (AD) treatment have garnered significant interest. Studies have reported the neuroprotective effects of Lico-A, suggesting its potential as a multitarget compound.

Metformin restores cognitive dysfunction and histopathological deficits in an animal model of sporadic Alzheimer's disease.

Background: Metformin has been introduced as a neuroprotective agent in recent years. Here we evaluate the therapeutic effects of metformin in sporadic mouse model of Alzheimer's disease (SAD).

Methods: AD was induced by streptozotocin (STZ, 0.

Under the umbrella of depression and Alzheimer's disease physiopathology: Can cannabinoids be a dual-pleiotropic therapy?

Depression and Alzheimer´s disease (AD) are two disorders highly prevalent worldwide. Depression affects more than 300 million people worldwide while AD affects 60-80% of the 55 million cases of dementia. Both diseases are affected by aging with high prevalence in elderly and share not only the main brain affected areas but also several physiopathological mechanisms.

Novel customized age-dependent corneal membranes and interactions with biodegradable nanoparticles loaded with dexibuprofen.

Ocular inflammation is one of the most prevalent diseases in ophthalmology and it is currently treated using eye drops of nonsteroidal antiinflammatory drugs such as dexibuprofen (DXI). However, their bioavailability is low and therefore, PLGA nanoparticles constitute a suitable approach to be administered as eyedrops. Therefore, DXI has been encapsulated into PLGA nanoparticles (DXI-NPs).

A novel rhein-huprine hybrid ameliorates disease-modifying properties in preclinical mice model of Alzheimer's disease exacerbated with high fat diet.

Background: Alzheimer's disease (AD) is characterized by a polyetiological origin. Despite the global burden of AD and the advances made in AD drug research and development, the cure of the disease remains elusive, since any developed drug has demonstrated effectiveness to cure AD. Strikingly, an increasing number of studies indicate a linkage between AD and type 2 diabetes mellitus (T2DM), as both diseases share some common pathophysiological features.

Extracellular vesicles, the emerging mirrors of brain physiopathology.

Extracellular vesicles are secreted by a wide variety of cells, and their primary functions include intercellular communication, immune responses, human reproduction, and synaptic plasticity. Their molecular cargo reflects the physiological processes that their cells of origin are undergoing. Thus, many studies have suggested that extracellular vesicles could be a promising biomarker tool for many diseases, mainly due to their biological relevance and easy accessibility to a broad range of body fluids.

Exosomes-Based Nanomedicine for Neurodegenerative Diseases: Current Insights and Future Challenges.

Neurodegenerative diseases constitute a group of pathologies whose etiology remains unknown in many cases, and there are no treatments that stop the progression of such diseases. Moreover, the existence of the blood-brain barrier is an impediment to the penetration of exogenous molecules, including those found in many drugs. Exosomes are extracellular vesicles secreted by a wide variety of cells, and their primary functions include intercellular communication, immune responses, human reproduction, and synaptic plasticity.

Application of the adverse outcome pathway to identify molecular changes in prenatal brain programming induced by IUGR: Discoveries after EGCG exposure.

Following a multi-disciplinary approach integrating information from several experimental models we have collected new evidence supporting, expanding and redesigning the AOP "Disrupted laminin/int-β1 interaction leading to decreased cognitive function". Investigations in vitro in rabbit and rat neurospheres and in vivo in mice exposed to EGCG (epigallocatechin-gallate) during neurodevelopment are combined with in vitro evaluations in neural progenitor cells overexpressing int-β1 and literature information from int-β1 deficiency models. We have discovered for the first time that neural progenitor cells from intrauterine growth restricted (IUGR) animals overexpress int-β1 at gene and protein level and due to this change in prenatal brain programming they respond differently than control neurospheres to the exposure of EGCG, a compound triggering neural progenitor cell migration alterations.

Protein tyrosine phosphatase 1B (PTP1B) as a potential therapeutic target for neurological disorders.

Protein tyrosine phosphatase 1B (PTP1B) is a typical member of the PTP family, considered a direct negative regulator of several receptor and receptor-associated tyrosine kinases. This widely localized enzyme has been involved in the pathophysiology of several diseases. More recently, PTP1B has attracted attention in the field of neuroscience, since its activation in brain cells can lead to schizophrenia-like behaviour deficits, anxiety-like effects, neurodegeneration, neuroinflammation and depression.

Peroxisomal Proliferator-Activated Receptor / Deficiency Induces Cognitive Alterations.

Peroxisome proliferator-activated receptor / (PPARβ/δ), the most PPAR abundant isotype in the central nervous system, is involved in microglial homeostasis and metabolism, whose disturbances have been demonstrated to play a key role in memory impairment. Although PPARβ/δ function is well-established in metabolism, its contribution to neuronal and specifically memory process is underexplored. Therefore, the aim of the study is to determine the role of PPARβ/δ in the neuropathological pathways involved in memory impairment and as to whether a risk factor implicated in memory loss such as obesity modulates neuropathological markers.

Impact of New Drugs for Therapeutic Intervention in Alzheimer's Disease.

The increases in population ageing and growth are leading to a boosting in the number of people living with dementia, Alzheimer's disease (AD) being the most common cause. In spite of decades of intensive research, no cure for AD has been found yet. However, some treatments that may change disease progression and help control symptoms have been proposed.

JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive function.

Background And Aim: The appearance of alterations in normal metabolic activity has been increasingly considered a risk factor for the development of sporadic and late-onset neurodegenerative diseases. In this report, we induced chronic metabolic stress by feeding of a high-fat diet (HFD) in order to study its consequences in cognition. We also studied the effects of a loss of function of isoforms 1 and 3 of the c-Jun N-terminal Kinases (JNK), stress and cell death response elements.

Targeting brain Renin-Angiotensin System for the prevention and treatment of Alzheimer's disease: Past, present and future.

Alzheimer's disease (AD) is a well-known neurodegenerative disease characterized by the presence of two main hallmarks - Tau hyperphosphorylation and Aβ deposits. Notwithstanding, in the last few years the scientific evidence about the drivers of AD have been changing and nowadays age-related vascular alterations and several cardiovascular risk factors have been shown to trigger the development of AD. In this context, drugs targeting the Renin Angiotensin System (RAS), commonly used for the treatment of hypertension, are evidencing a high potential to delay AD development due to their action on brain RAS.

Development of Peptide Targeted PLGA-PEGylated Nanoparticles Loading Licochalcone-A for Ocular Inflammation.

Licochalcone-A is a natural compound with anti-inflammatory properties. However, it possesses low water solubility, making its application for the treatment of ocular inflammation difficult. To overcome this drawback, biodegradable nanoparticles incorporating Licochalcone-A have been developed.